The instant invention provides for substituted thiazoles that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 277/20 - Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
Disclosed is a method for predicting the sensitivity of a cancer cell to a PLK1 inhibitor. Also disclosed is a method for predicting the RB status of a cancer cell. The sensitivity to a PLK1 inhibitor or the RB status can be predicted through the following steps: determining the expression level of cyclin D1 gene and the expression level of p16 gene in a biological sample collected from a patient; determining the ratio of the expression level of cyclin D1 gene to the expression level of p16 gene; and predicting that the PLK1 inhibitor is effective or the RB function is abnormal when the ratio of the expression levels is smaller compared with that in a control cell.
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
The invention relates to a compound of a general formula (I): wherein A represents a linking group; Ar1 represents a group formed from an aromatic ring; R1 and R2 each independently represent a hydrogen atom, a halogen atom, a cyano group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, a halo-C1-C6 alkoxy group, a cyclo-C3-C6 alkyloxy group, a C2-C7 alkanoyl group, a halo-C2-C7 alkanoyl group, a C2-C7 alkoxycarbonyl group, a halo-C2-C7 alkoxycarbonyl group, a cyclo-C3-C6 alkyloxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-C1-C6 alkoxy group, a carboxy-C2-C6 alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb; a C1-C6 alkyl group optionally having substituent(s); an aryl or heterocyclic group optionally having substituent(s); or a C1-C6 alkyl group or a C2-C6 alkenyl group having the aryl or heterocyclic group; T and U each independently represent a nitrogen atom or a methine group; and V represents an oxygen atom, a sulfur atom or an imino group. The compound of the invention is useful as therapeutical agents for various ACC-related diseases.
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
Disclosed is a melanin-concentrating hormone receptor antagonist which is useful as a pharmaceutical product for central nervous system diseases, cardiovascular diseases and metabolic diseases. A compound represented by formula (I) [wherein R1a and R1b each represents a hydrogen atom or the like; R2 represents a hydrogen atom, a C1-6 alkyl or the like; Ar1 represents a six-membered aromatic carbocyclic group or a six-membered aromatic nitrogen-containing heterocyclic group; Ar2 represents a group obtained by removing two hydrogen atoms from a six-membered aromatic carbocycle, a six-membered aromatic nitrogen-containing heterocycle or the like; Ar3 represents a monocyclic or bicyclic aromatic carbocycle or aromatic heterocycle; and m1, m2, m3 and m4 independently represent 0, 1, 2, 3 or 4, provided that the total of m1 and m2 is not less than 2 but not more than 6 and the total of m3 and m4 is not less than 2 but not more than 6] is disclosed. The compound is useful as a pharmaceutical product for central nervous system diseases, cardiovascular diseases and metabolic diseases.
A61K 31/4427 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present invention relates to a process for producing a hydrate of 3-(2,6-dichlorophenyl)-4-imino-7-[(2'-methyl-2',3'-dihydro-1'H-spiro[cyclopropane-1,4'-isoquinolin]-7'-yl)amino]-3,4-dihydropyrimido[4,5-d] pyrimidin-2(1H)-one (Compound A) or of a pharmaceutically acceptable salt of Compound A and a crystalline form of Compound A or of a pharmaceutically acceptable salt of Compound A, which are useful in the field of treatment of various cancers as a kinase inhibitor, especially as a Weel kinase inhibitor.
The instant invention provides for substituted [1,2,4]triazolo[4,3-a]-1,5-naphthyridine compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms, preferably Akt1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity, especially Akt1 by administering the compound to a patient in need of treatment of cancer.
A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
Disclosed is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, which has an agonistic activity on GPR120 and is therefore useful for the treatment of diabetes, obesity or hyperlipemia. [In formula (I), the A represents a phenyl group which may be substituted by a lower alkoxy group or the like, or the like; the B represents a bivalent group produced by removing two hydrogen atoms from a benzene ring which may be substituted by a halogen atom or the like, or the like; X represents a lower alkylene group having 2 to 4 carbon atoms in its main chain or the like, wherein a carbon atom constituting the main chain may be substituted by an oxygen atom or the like; and Y represents a hydrogen atom or the like.]
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
The instant invention provides for substituted naphthyridine compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms, preferably Akt1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity especially Akt1 by administering the compound to a patient in need of treatment of cancer.
Disclosed is a compound useful as a prophylactic agent or a therapeutic agent for cardiovascular diseases, nervous system diseases, metabolic diseases, genital diseases, gastrointestinal diseases, neoplasm, infectious diseases and others or an herbicide. Specifically disclosed is a long-chain fatty acid elongation enzyme inhibitor comprising a compound represented by formula (I) [wherein W represents a hydrogen atom, a C1-6 alkyl or the like; X represents an aryl, a heteroaryl or the like; n represents a number of 0 or 1; Z represents a hydrogen atom, a C1-6 alkyl or the like; and A1, A2, A3 and A4 independently represent CH or N] or a pharmaceutically acceptable salt thereof as an active ingredient.
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 31/197 - Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid (GABA), beta-alanine, epsilon-aminocaproic acid, pantothenic acid
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 3/12 - Drugs for disorders of the metabolism for electrolyte homeostasis
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 15/08 - Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07C 311/16 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
C07C 317/44 - Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
C07D 209/52 - Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
C07D 217/02 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 235/14 - Radicals substituted by nitrogen atoms
C07D 265/30 - 1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
C07D 295/20 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 453/06 - Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing iso-quinuclidine ring systems
Disclosed is a method for the screening of a therapeutic agent for cancer in which Hedgehog pathway is activated by using a molecule involved in Hedgehog pathway. Also disclosed is a method for determining the occurrence of the activation of Hedgehog pathway in a cancer cell particularly collected from a subject. A substance which can cause the change in the expression level or activity of p70S6K2 or the phosphorylation state of GSK3β that is a substrate for p70S6K2 is selected as a pharmaceutical candidate substance for the treatment of cancer in which Hedgehog pathway is activated. By elucidating the expression level or activity of p70S6K2 or the phosphorylation state of GSK3β in a cell, the activation state of Hedgehog pathway can be determined.
Disclosed is an antagonist of a melanin-concentrating hormone receptor, which is useful as a medicinal agent for central nervous system diseases, cardiovascular diseases and metabolic diseases. Specifically disclosed is a diarylmethylamide derivative represented by formula (I) [wherein R1a, R1b, R2a, R2b, R3a and R3b independently represent a hydrogen atom or the like; R4 represents a hydrogen atom, a C1-6 alkyl or the like; R5 represents a hydrogen atom or the like; Z represents a C1-6 alkyl or the like, or R4 and Z together form a nitrogenated 4- to 6-membered hetero ring; Y1 represents H or the like and Y2 represents H, or Y1 and Y2 together form -O-CH2-; W represents C, SO or the like; Ar1 represents a 6-membered aryl or the like; Ar2 represents a 6-membered aryl or the like; and ring A represents a benzene ring, a pyridine ring or the like].
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/5025 - Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 3/12 - Drugs for disorders of the metabolism for electrolyte homeostasis
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 15/08 - Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Disclosed is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof, which has an antagonistic activity on a neuropeptide Y receptor and is therefore useful for the treatment of hypertension, arteriosclerosis, bulimia, obesity or the like. [In formula (I), R1 represents a hydrogen atom, a cyano group, or the like; R represents a group represented by formula (II); X1 represents a lower alkylene group having 1 to 4 carbon atoms, or the like; X2 represents a lower alkylene group, or the like; and Het represents a 5-membered aromatic heterocyclic ring having at least one nitrogen atom andalso having one or two hetero atoms independently selected from a nitrogen atom, a sulfur atom and an oxygen atom.]
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61K 31/541 - Non-condensed thiazines containing further heterocyclic rings
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 451/02 - Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane; Cyclic acetals thereof
The present invention relates to a compound of formula I:wherein: R1 is a hydrogen atom, F, CN, etc.; R2 is CO, SO2, etc.; R3 is a phenyl which may be substituted; X1, X2, and X3 each independently CH, N, etc. provided, however, that among X1, X2 and X3, the number of nitrogen is 0 or 1; W is the following residue:wherein: W1, W2, and W3 each independently CH, N, etc.,or a pharmaceutically acceptable salt or ester thereof.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 41/00 - Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Disclosed is a compound which is useful as a prophylactic or therapeutic agent for cardiovascular diseases, nervous system diseases, metabolic diseases, genital diseases and gastrointestinal diseases. Specifically disclosed is a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof. (I) wherein Z represents a group represented by Formula (II-1), (II-2) or (II-3) shown below; n1, n2 and n3 independently represent a numeral value of 0, 1 or 2; R1 represents a C1-6 alkyl, a C3-8 cycloalkyl or the like; R2 represents an aryl or a heteroaryl; R3 represents a hydrogen atom, a C1-6 alkyl or the like; and M1, M2, M3 and M4 independently represent a hydrogen atom, a C1-6 alkyl or the like, or M1 and M2, M3 or M4 together form a group -CH2- or the like.
C07D 211/26 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 15/08 - Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 453/06 - Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing iso-quinuclidine ring systems
Disclosed is a compound represented by the formula (I) below or a pharmaceutically acceptable salt thereof, which has glucokinase activating activity and is thus useful for treatment of diabetes, obesity and the like. (In the formula, R1 and R2 independently represent a lower alkyl group; X represents CH or the like; and X1 represents an aminoalkoxy group or the like.)
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A compound that is useful as an agent in the prevention and treatment of circulatory system, nervous system, metabolic, reproductive system, and gastrointestinal diseases. Formula (I) is a compound represented by the following: [structure 1] [wherein, Z represents formula (II-1), (II-2), or (II-3), [structure 1] m and n are 0, 1, or 2, Y represents CR3 or N, R1 represents a C1-6 alkyl, C3-8 cycloalkyl, etc., R2 represents phenyl or a heteroaryl, etc., R3 and R4 each independently represent a hydrogen atom, a C1-6 alkyl, etc., M1, M2, M3, and M4 each independently represent a hydrogen atom, a C1-6 alkyl, etc.]
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 3/12 - Drugs for disorders of the metabolism for electrolyte homeostasis
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
C07D 277/20 - Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
C07D 285/125 - 1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
Disclosed is a compound represented by the formula (I) below or a pharmaceutically acceptable salt thereof, which has a glucokinase activating effect and is thus useful for treatment of diabetes, obesity and the like. (In the formula (I), ring A represents a pyrazolyl group which may have a lower alkyl group or the like; ring B represents a heteroaryl group; R represents a lower alkyl group or the like; R1 represents a group represented by the formula (II-1) below or the like; R2 represents a lower alkyl group or the like; r represents an integer of 0-3; and k represents an integer of 0-4.) (In the formula (II-1), R11 and R12 independently represent a hydrogen atom or the like; and m represents an integer of 2-6.)
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 25/00 - Drugs for disorders of the nervous system
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
Disclosed are: a compound represented by the formula (I-0); and others. (I-0) wherein R1 represents a C1-C6 alkyl group, a C2-C6 alkenyl group, a C2-C6 alkynyl group or a C3-C6 cycloalkyl group; R2, R3, R4 and R5 independently represent a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6-alkyl group, a C1-C6 alkoxy group or a halo-C1-C6-alkoxy group; R6 represents a hydrogen atom or a C1-C6 alkyl group; R7a represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6-alkyl group, a C1-C6 alkoxy group, a hydroxy-C1-C6-alkyl group, -Q2-N(R1c)R1d or a nitrogenated heterocyclic group; R8a represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halo-C1-C6-alkyl group, a C1-C6 alkoxy group or a hydroxy-C1-C6-alkyl group; or R7a and R8a may together form a C2-C6 alkylene group, or R7a, R8a and a ring atom to which R7a and R8a are attached may together form a spiro ring or a bicyclo ring; and X and Y independently represent a methine group or a nitrogen atom. The compound has an excellent inhibitory activity on Wee1 kinase and therefore exhibits an inhibitory activity on the proliferation of a cell and an additive/synergistic effect with a different anti-cancer agent. Therefore, the compound is useful in the medical field.
A61P 35/02 - Antineoplastic agents specific for leukemia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
[PROBLEMS] To provide a compound useful as an agent for the treatment of circulatory diseases, nervous system diseases, metabolic diseases, reproductive system diseases, and digestive tract diseases. [MEANS FOR SOLVING PROBLEMS] The compound, which is for use as an active ingredient, is represented by the formula (I): [wherein R1 represents optionally halogenated C1-6 alkyl, etc.; R2 represents, e.g., a group represented by the formula (II-1) or (II-4) (wherein W represents C1-6 alkylene, etc. and R represents C1-6 alkyl, etc.); R3 represents hydrogen, C1-6 alkyl, etc.; X represents -O-, -NH-, etc.; and Y1, Y2, Y3, and Y4 each independently represents -CH-, -N-, etc.].
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/536 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with carbocyclic ring systems
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 15/00 - Drugs for genital or sexual disorders; Contraceptives
A61P 15/08 - Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 15/10 - Drugs for genital or sexual disorders; Contraceptives for impotence
A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/02 - Drugs for disorders of the nervous system for peripheral neuropathies
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 265/18 - 1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in position 2
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
Disclosed is a method for commercially producing a pyrazol-3-yl-benzamide derivative represented by the formula below, which is useful as a pharmaceutical product, efficiently. (In the formula, R2, R3 and R4 independently represent a lower alkyl group.)
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 213/71 - Sulfur atoms to which a second hetero atom is attached
[PROBLEMS] To provide an antagonist of a melanin-concentrating hormone receptor, which is useful as a medicine for a central nervous system disease, a cardiovascular disease or a metabolic disease. [MEANS FOR SOLVING PROBLEMS] The antagonist comprises, as an active ingredient, a compound represented by the formula (I). (I) wherein R1a and R1b independently represent a hydrogen atom or a C1-6 alkyl group; R2a, R2b, R3a and R3b independently represent a hydrogen atom, a C1-6 alkyl group, or the like; Y represents H or -OH; Z represents -OR8, or the like; R8 represents a hydrogen atom, a C1-6 alkyl group which may have a substituent, or the like; R9a and R9b independently represent a hydrogen atom, a C1-6 alkyl group, or the like; Ar1 represents an aromatic carbon ring group, or an aromatic heteroring group; Ar2 represents a group produced by removing two hydrogen atoms from an aromatic carbon ring, or the like; and the ring group A represents an unsaturated heteroring group.
C07D 211/26 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms
A61K 31/451 - Non-condensed piperidines, e.g. piperocaine having a carbocyclic ring directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/5025 - Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 211/52 - Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 451/04 - Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring system
[PROBLEMS] To provide compounds useful as prophylatic or therapeutic agents for circulatory diseases, nervous diseases, metabolic diseases, reproductive system diseases, and digestive diseases. [MEANS FOR SOLVING PROBLEMS] Compounds represented by the general formula (I) or pharmaceutically acceptable salts thereof: wherein R1 is C1-6 alkyl, C3-8 cycloalkyl, or the like; R2 is phenyl, heteroaryl, or the like; Q is N or CH; and M1, M2, M3 and M4 are each independently hydrogen or C1-6 alkyl, or alternatively M1 together with M2 or M3 forms -CH2-CH2- or the like, or M4 together with M2 or M3 forms -CH2-CH2- or the like, with the proviso that M1, M2, M3, and M4 are such that one -CH2- or -CH2-CH2- group is formed thereamong.
C07D 451/04 - Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.02,4] nonane ring system
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
Disclosed are: a compound represented by the general formula (I); and others. (I) wherein A1 and A2 independently represent a nitrogen atom or a methine group which may be substituted; the ring B represents a 5- to 7-membered aliphatic ring or a spiro or bicyclo ring formed by the aliphatic ring and a 3- to 7-membered aliphatic ring which is different from the aforementioned aliphatic ring; R1 represents a hydrogen atom, a C1-C6 alkyl group which may be substituted or an aryl, aralkyl or heteroaryl group which may be substituted; R2 represents an aryl, aralkyl or heteroaryl group which may be substituted; and X represents a group represented by the formula =NH or =O. The compound has an excellent cell proliferation inhibition activity relying on a Wee1 kinase inhibition activity and an additive/synergistic effect with other anti-cancer agent, and is therefore useful in the medical field.
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
25.
POLYMORPH OF DIHYDROPYRAZOLOPYRIMIDINONE DERIVATIVE AS WEEL KINASE.INHIBITOR
The present invention relates to the crystalline forms of 2-allyl-l -[6-(I -hydroxy- 1 methylethyl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-l-yl)phenyl]amino}-l,2-dihydro-3H- pyrazolo[3,4-d]pyrirnidin-3-one or a salt thereof, which are useful in the field of treatment of various cancers as a kinase inhibitor, especially as a Weel kinase inhibitor.
A compound represented by the general formula (I-a): (I-a) [wherein R1a and R2a each means hydrogen, lower cycloalkyl, lower alkyl, etc.; R3a means hydrogen, lower cycloalkyl, lower alkyl, etc.; R4a and R5a each means lower alkyl, lower cycloalkyl, etc. or R4a and R5a are bonded to each other to form lower cycloalkylidene; and R6a means lower alkyl, lower haloalkyl, etc.]. This compound functions as an LCE inhibitor and is useful as a therapeutic agent for various circulatory diseases, nervous diseases, metabolic diseases, reproductive diseases, digestive tract diseases, neoplasm, infectious diseases, etc.
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 3/12 - Drugs for disorders of the metabolism for electrolyte homeostasis
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 5/50 - Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 15/00 - Drugs for genital or sexual disorders; Contraceptives
A61P 15/08 - Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 15/10 - Drugs for genital or sexual disorders; Contraceptives for impotence
A61P 17/02 - Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
A61P 25/00 - Drugs for disorders of the nervous system
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
It is intended to find a kinase whose expression is increased in cancer cells and which is involved in the Wnt pathway and to enable the evaluation (for example, screening) of a compound having an effect of treating or preventing a disease (for example, cancer) caused by an abnormality of the Wnt pathway using the kinase. A method for evaluating a compound effective in the treatment of a disease caused by an abnormality of the Wnt pathway, characterized by comprising the steps of: bringing a test compound into contact with MARK4 protein; measuring a kinase activity of the MARK4 protein; comparing the activity with a kinase activity of the MARK4 protein in the absence of contact with the test compound and selecting the test compound which decreases the kinase activity of the MARK4 protein, and an MARK4 inhibitor screened by the evaluation method.
[PROBLEMS] To provide: a gene-modified non-human animal having inactivated MGAT2 gene, which is useful for the search of the function of MGAT2 in vivo; a gene-modified non-human animal cell; a method for screening of a compound capable of inhibiting the activity of MGAT2; a compound capable of inhibiting the activity of MGAT2; and a method for detecting a disease induced by abnormal lipid metabolism based on the expression level or activity of MGAT2. [MEANS FOR SOLVING PROBLEMS] Disclosed are: a gene-modified non-human mammal having the artificially inhibited expression of MGAT2 gene; and a method for screening of a compound by using the mammal. The mammal and the method enable to prevent or treat a disease induced by abnormal lipid metabolism. Also disclosed is the screening of a compound capable of inhibiting or enhancing the function of MAGT2. The screening enables to prevent or treat a disease induced by abnormal lipid metabolism.
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 1/18 - Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
The invention relates to a compound of a general formula (I): (I) wherein Ar1 represents a group formed from an aromatic ring selected from a group consisting of indole, 1H-indazole, 2H-indazole, 1H-thieno[2,3-c]pyrazole, 1H-pyrazolo[3,4-b]pyridine, benzo[b]furan, benzimidazole, benzoxazole, 1,2-benzisoxazole and imidazo[1,2-a]pyridine; R1 and R2 each represent a hydrogen atom, a halogen atom, a cyano group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, a halo-C1-C6 alkoxy group, a cyclo-C3-C6 alkyloxy group, a C2-C7 alkanoyl group, a halo-C2-C7 alkanoyl group, a C2-C7 alkoxycarbonyl group, a halo-C2-C7 alkoxycarbonyl group, a cyclo-C3-C6 alkyloxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-C1-C6 alkoxy group, a carboxy-C2-C6 alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb; an optionally-substituted C1-C6 alkyl, aryl or heterocyclic group; or a C1-C6 alkyl or C2-C6 alkenyl group having the aryl or heterocyclic group; R3 and R4 each represent a hydrogen atom, a halogen atom, a nitro group, a cyclo-C3-C6 alkyl group, a carbamoyl group optionally substituted with a C1-C6 alkyl or cyclo-C3-C6 alkyl group, or a group of -N(Re)Rf; an optionally-substituted C2-C7 alkanoyl, C1-C6 alkoxy, C2-C7 alkoxycarbonyl, cyclo-C3-C6 alkyloxycarbonyl, C1-C6 alkylsulfonyl, C1-C6 alkylthio, cyclo-C3-C6 alkyloxy, cyclo-C3-C6 alkyl-C1-C6 alkoxy, cyclo-C3-C6 alkylsulfonyl, cyclo-C3-C6 alkylthio or cyclo-C3-C6 alkyl-C1-C6 alkylthio group; or an optionally-substituted C1-C6 alkyl group; T and U each represent a nitrogen atom or a methine group; and V represents an oxygen atom or a sulfur atom. The compound of the invention is useful as therapeutical agents for various ACC-related diseases.
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
The invention relates to a compound of a general formula (I): wherein Ar1 represents a group formed from an aromatic ring selected from a group consisting of indole, benzimidazole and 1,2-benzisoxazole, having R3 and R4, and optionally having a substituent selected from a group consisting of a halogen atom, a hydroxyl group, a C1-C6 alkyl group, a halo-C1-C6 alkyl group, a hydroxy-C1-C6 alkyl group, a cyclo-C3-C6 alkyl group, a C1-C6 alkoxy group, a halo-C1-C6 alkoxy group and carbamoyl group; R1 represents a phenyl group optionally substituted with a carboxyl group, a tetrazolyl group optionally substituted with a C2-C7 alkanoyloxy-C1-C6 alkyl group, a pyridyl group optionally substituted with a C1-C6 alkyl group or a carboxyl group, a dihydro-1,2,4-triazolyl group optionally substituted with an oxo group, or a dihydro-1,2,4-oxadiazolyl group optionally substituted with an oxo group; R2 represents a hydrogen atom, a halogen atom, a C1-C6 alkyl group, or a C1-C6 alkoxy group; and R3 and R4 each independently represent a hydrogen atom, a halogen atom, nitro group, a cyclo-C3-C6 alkyl group, a carbamoyl group optionally substituted with a C1-C6 alkyl or cyclo-C3-C6 alkyl group, a C1-C6 alkoxy group optionally substituted with a hydroxyl group, or a C1-C6 alkyl group optionally substituted with a hydroxyl group. The compound of the invention is useful as therapeutical agents for various ACC-related diseases.
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
The invention relates to a compound of a general formula (I): wherein Ar1 represents a group formed from an aromatic ring selected from a group consisting of benzene, pyrazole, isoxazole, pyridine, indole, 1H-indazole, 1H-furo[2,3-c]pyrazole, 1H-thieno[2,3-c]pyrazole, benzimidazole, 1,2-benzisoxazole, imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine and 1H-pyrazolo[3,4-b]pyridine, having Ar2, and optionally having one or two or more substituents selected from R3; R1 and R2 each independently represent a hydrogen atom, a halogen atom, a cyano group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, a C2-C7 alkanoyl group, a C2-C7 alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-C1-C6 alkoxy group, a carboxy-C2-C6 alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb; or a C1-C6 alkyl group optionally having a substituent; or an aryl or heterocyclic group optionally having a substituent; or a C1-C6 alkyl group or a C2-C6 alkenyl group having the aryl or heterocyclic group; T and U each independently represent a nitrogen atom or a methine group; and V represents an oxygen atom or a sulfur atom. The compound of the invention is useful as therapeutical agents for various ACC-related diseases.
A01N 43/16 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atom with one hetero atom six-membered rings with oxygen as the ring hetero atom
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
32.
NOVEL AMINOPYRIMIDINE DERIVATIVE AS PLK1 INHIBITOR
Disclosed is a compound represented by the general formula (I) below, or a pharmaceutically acceptable salt or ester thereof. (In the formula, R1 and R2 may be the same or different and represent a hydrogen atom, a lower alkyl group, a cycloalkyl group or the like; R3 and R4 may be the same or different and represent a hydrogen atom, a lower alkyl group, an NRaRb, a phenyl group, a lower alkyl group substituted with a phenyl group, a 4- or 7-membered aliphatic heterocyclic group, a lower alkyl group substituted with a 4- or 7-membered aliphatic heterocyclic group, a 5- or 6-membered aromatic heterocyclic group, a lower alkyl group substituted with a 5- or 6-membered aromatic heterocyclic group or the like; and R5 represents a hydrogen atom, a cyano group, a halogen atom or a lower alkyl group.)
The present invention relates to a compound represented by Formula [I]: or a pharmaceutically acceptable salt or ester thereof, wherein R1 and R2, which may be the same or different, are each a hydrogen atom, a halogen atom, a lower alkyl group which may be substituted, or a cyclopropyl group; R3 and R4, which may be the same or different, are each a hydrogen atom, a lower alkyl group substituted with NRaRb, a 4- to 6-membered aliphatic heterocyclic group, a lower alkyl group substituted with a 4- to 6-membered aliphatic heterocyclic group, a 5- or 6-membered aromatic heterocyclic group, or a lower alkyl group substituted with a 5- or 6-membered aromatic heterocyclic group; and R5 is a hydrogen atom, a cyano group, a halogen atom, or a lower alkyl group.
The instant invention provides for substituted naphthyridine compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 407/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4353 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
Disclosed is a compound represented by the formula (I) below, which has GPR120 agonist activity and thus is useful for treatment of diabetes or hyperlipemia, or a pharmaceutically acceptable salt thereof. (In the formula, (AA) represents a phenyl group which may be substituted with a lower alkoxy group or the like, or the like; (BB) represents a divalent group obtained by removing two hydrogen atoms from a benzene ring which may be substituted with a halogen atom or the like, or the like; X represents a spacer having a main chain composed of 1-8 carbon atoms wherein 1-3 carbon atoms in the main chain may be substituted with an oxygen atom or the like; and Y represents a hydrogen atom or the like.)
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
Disclosed is a compound represented by the following formula (I). [chemical formula 1] (I) (In the formula, R1a and R1b may be the same or different and represent a hydrogen atom or the like; R2a and R2b may be the same or different and represent a hydrogen atom or the like, or alternatively R2a and R2b may combine together to form -CH2CH2- or the like; R3a and R3b may be the same or different and represent a hydrogen atom or the like, or alternatively R3a and R3b may combine together to form -CH2CH2- or the like; Y1 and Y2 respectively represent -C(R)2- or the like; Z represents OR and R represents a hydrogen atom, a C1-6 alkyl group or the like; Ar1 represents a six-membered aromatic carbon ring group or the like; Ar2 represents a six-membered aromatic carbon ring group or the like; and A3 represents a six-membered aromatic carbon ring or the like. This compound is useful as a pharmaceutical product for central nervous system diseases, cardiovascular diseases and metabolic diseases.
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Disclosed is a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof, which has a glucokinase-activating activity and is therefore useful for the treatment of diabetes or obesity. (I) wherein R1 and R2 independently represent a lower alkyl group; and X1 represents a group represented by the formula (II-1): (II-1) where R11 and R12 independently represent a hydrogen atom or a lower alkyl group, or R11 and R12 together with a nitrogen atom to which R11 and R12 are bonded may form a 4- to 7-membered nitrogenated aliphatic ring (wherein one of the carbon atoms constituting the 4- to 7-membered nitrogenated aliphatic ring may be substituted by an oxygen atom), or R11 and R12 together with any carbon atom in the group (CH2)m may form a 4- to 7-membered nitrogenated aliphatic ring or the like; and m represents an integer of 1 to 3.
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
[PROBLEMS] To provide: a gene marker or a protein marker for detecting whether or not an Aurora A inhibitor acts in a living body in an Aurora A-specific manner when the Aurora A inhibitor is administered to the living body; and a method for predicting or diagnosing the pharmacological efficacy of an Aurora A inhibitor by using the gene marker or the protein marker. [MEANS FOR SOLVING PROBLEMS] A gene/protein marker for use in the prediction or diagnosis of the pharmacological efficacy of an Aurora A inhibitor, wherein the gene is a gene selected from the group consisting of Aurora B, Histone H3, BIRC5, PRC1, DLG7, TACC3 and KNTC2 or a gene having substantially the same function as that of the gene; and a method for predicting or diagnosing the pharmacological efficacy of an Aurora A inhibitor by using the gene/protein marker.
G01N 37/00 - INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES - Details not covered by any other group of this subclass
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A compound represented by the formula (I). (I) wherein R1a and R1b independently represent a hydrogen atom or the like; R2a and R2b independently represent a hydrogen atom or the like, or together form -CH2CH2- or the like; R3a and R3b independently represent a hydrogen atom or the like, or together form -CH2CH2- or the like; Y1 and Y2 independently represent -C(R)2- or the like; Z represents OR, NR2 or the like; R represents a hydrogen atom, a C1-6 alkyl group or the like; Ar1 represents a 6-membered aromatic hydrocyclic group or the like; Ar2 represents a 6-membered aromatic hydrocyclic group or the like; and A3 represents a 6-membered aromatic hydrocyclic group or the like. The compound is useful as a pharmaceutical agent for a central nervous system disease, a cardiovascular disease or a metabolic disease.
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Intended is to acquire a high yield of an object substance and to retain a high productivity. A reaction apparatus (10) comprises a main passage (12) of an internal diameter of 3 mm for a raw material (M1) to flow therein, an inlet passage (14) for a raw material (M2) to react chemically with the raw material (M1) and to flow therein, and five branch inlet passages (16a - 16e) branching from the inlet passage (14) for introducing the raw material (M2) into the main passage (12) at predetermined inlet points (12o - 12s) in the main passage (12). In this main passage (12), the length of passages (12b - 12d) of the adjoining inlet points (12p - 12s) is made equal to or less than the length of the passages (12a - 12c) between the adjoining inlet points (12o - 12r) just ahead in the flow direction of the raw material (M1). Moreover, the length of passages (12b - 12d) of at least one adjoining inlet points (12p - 12s) is made shorter than the length of the passages (12a - 12c) between the adjoining inlet points (12o - 12r) ahead in the flow direction of the raw material (M1).
B01J 19/24 - Stationary reactors without moving elements inside
C07C 67/343 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms
It is intended to find a target gene for an antitumor agent effective specifically in a cancer cell caused by abnormality of p53 or PI3 kinase, and to realize the evaluation of a compound using the gene. A method for evaluating a compound effective in the treatment of cancer characterized by comprising the steps of: preparing a cell expressing PKC-iota by introducing a PKC-iota gene; bringing a test compound into contact with the cell; and detecting a specific binding of the test compound to the PKC-iota. A method for evaluating a compound having the step of measuring the activity or expression level of an intracellular signal transducer induced by the contact instead of the detection step.
The present invention relates to a compound of general formula I: wherein: R1 is a hydrogen atom, F, CN, etc.; R2 is O, S, SO, SO2, etc.; R3 is a phenyl which may be substituted; X2 is CH, N, etc.; W is the following residue: wherein: W1, W2, and W3 each independently CH, N, etc., or a pharmaceutically acceptable salt or ester thereof.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 35/02 - Antineoplastic agents specific for leukemia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
43.
NOVEL AMINOPYRIDINE DERIVATIVE HAVING AURORA A-SELECTIVE INHIBITORY ACTIVITY
Disclosed is a compound represented by the general formula [I] below or a pharmaceutically acceptable salt or ester thereof. (I) (In the formula, R1 represents a hydrogen atom, F, CN or the like; R1' represents a hydrogen atom or an optionally substituted lower alkyl group; R2 represents O, S, SO, SO2 or the like;R3 represents an optionally substituted phenyl group; X1, X2 and X3 independently represent CH, N or the like, provided that none or one of X1, X2 and X3 is N; and W represents a group represented by the following formula: , wherein W1, W2 and W3 independently represent CH, N or the like.)
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 35/02 - Antineoplastic agents specific for leukemia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
44.
PROCESS FOR MAKING LACTAM TACHYKININ RECEPTOR ANTAGONISTS
The present invention is directed to a process for preparing α,α disubstituted &ggr;-lactam derivatives of formula (I) that are useful as neurokinin-1 (NK-1) receptor antagonists, and inhibitors of tachykinin and in particular substance P. The compounds are useful in the treatment of certain disorders, including emesis, urinary incontinence, depression, and anxiety.
C07D 207/273 - 2-Pyrrolidones with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
45.
METHOD FOR PRODUCING &bgr;-DIARYL ELECTRON-WITHDRAWING GROUP SUBSTITUTED COMPOUND
NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY (Japan)
BANYU PHARMACEUTICAL CO., LTD. (Japan)
Inventor
Miyaura, Norio
Yamamoto, Yasunori
Nishikata, Takashi
Itoh, Takahiro
Abstract
Disclosed is a method for producing a &bgr;-diaryl electron-withdrawing group substituted compound at high yield with high selectivity. Specifically, an optically active &bgr;-diaryl electron-withdrawing group substituted compound represented by the general formula (V) below is produced by reacting an electron-withdrawing group substituted-&bgr;-arylolefin derivative represented by the general formula (I) below with an arylboron represented by the following general formula (II): Ar2-BXmMn in the presence of a compound represented by the following general formula (IV): RhYoL1p(Chiraphos)q (wherein Y represents ClO4, BF4, PF6, SbF6, OTf, a halogen atom, a hydroxy group, an alkoxy group or an acyloxy group, and L1 represents an organic ligand). [chemical formula 1] (I) (In the formula, Ar1 represents an aryl group, and E represents a formyl group, an acyl group or the like.) [chemical formula 3] (V)
C07C 45/68 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of C=O groups by change of size of the carbon skeleton by increase in the number of carbon atoms
C07C 49/213 - Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing six-membered aromatic rings
C07C 49/255 - Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
C07C 49/35 - Saturated compounds containing keto groups bound to rings containing ether groups, groups, groups, or groups
C07C 67/343 - Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by change of size of the carbon skeleton by increase in the number of carbon atoms
C07C 221/00 - Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
C07C 225/22 - Compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly-bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
C07D 317/60 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 405/06 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Disclosed is a compound represented by the formula (I) which can be used as an active ingredient: (I) wherein Az represents an azetidinyl group which may have a substituent; L represents a single bond or a C1-C2 alkylene group which may optionally have a substituent; and Ar represents a phenyl group which may optionally have a substituent or a pyridyl group which may optionally have a substituent. The compound is useful as an antagonist for a melanin-concentrating hormone receptor and is therefore useful as a pharmaceutical agent for a central nervous system disease, a cardiovascular disease or a metabolic disease.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/4427 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 3/12 - Drugs for disorders of the metabolism for electrolyte homeostasis
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 15/00 - Drugs for genital or sexual disorders; Contraceptives
A61P 15/08 - Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 15/10 - Drugs for genital or sexual disorders; Contraceptives for impotence
A61P 17/16 - Emollients or protectives, e.g. against radiation
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/02 - Drugs for disorders of the nervous system for peripheral neuropathies
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
The present invention relates to a method of treating cancer in a subject in need thereof, by administering to a subject in need thereof a first amount of an Aurora kinase inhibitor or a pharmaceutically acceptable salt or hydrate thereof, in a first treatment procedure, and a second amount of an anti-cancer agent in a second treatment procedure. The first and second amounts together comprise a therapeutically effective amount. The effect of the Aurora kinase inhibitor and the anti-cancer agent may be additive or synergistic.
The invention relates to compounds of a general formula (I): wherein A1 is selected from the following formula (aa1); R1 is a lower alkenyl group or a lower alkynyl group; R2 is a phenyl, pyridyl or thienyl group; R5 and R6 are a hydrogen atom, a lower alkyl group or a hydroxy-lower alkyl group, etc. The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.
Disclosed is a compound represented by the general formula (I) or a pharmaceutically acceptable salt or ester thereof: (I) wherein n1 and n2 independently represent 0 or 1; R represents an aryl group, a heteroaryl group or the like; Re represents a hydrogen atom or a lower alkyl group; two groups selected from the group consisting of the four groups (i) to (iv) below together form a group –(CH2)n- [wherein n represents 1, 2 or 3]: (i) one of Ra1 and Ra1', (ii) one of Ra2 and Ra2', (iii) one of Rb1 and Rb1', and (iv) one of Rb2 and Rb2', and groups not involved in the formation of the group –(CH2)n- among Ra1, Ra1', Ra2, Ra2', Rb1, Rb1', Rb2 and Rb2' independently represent a hydrogen atom or the like; Rc, Rd and Re independently represent a hydrogen atom or the like; X1, X2, X3 and X4 independently represent CH, N or the like; Y1, Y2 and Y3 independently represent CH or N; and W represents a 5-membered aromatic heterocyclic ring.
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/4995 - Pyrazines or piperazines forming part of bridged ring systems
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 45/08 - Mixtures of an active ingredient and an auxiliary substance neither being chemically characterised, e.g. antihistaminicum and surface active substance
Disclosed is a compound represented by the following general formula (I) or the like. (I) (In the formula, Ar1 represents an optionally substituted aryl group or heteroaromatic ring group; R1 represents an optionally substituted lower alkyl group, lower alkenyl group, lower alkynyl group or cyclo-lower alkyl group, or alternatively an optionally substituted aryl group, aralkyl group or heteroaromatic ring group; R2 represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or alternatively an optionally substituted aryl group, aralkyl group or heteroaromatic ring group; R3 represents a hydrogen atom or a lower alkyl group; R4 represents a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group represented by -N(R1k)R1m; and T and U respectively represent a nitrogen atom or a methine group.) This compound has an excellent Wee1 kinase inhibitory activity, and thus is useful in the field of pharmaceutical products, particularly in the field of drugs for treating various cancers.
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/54 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
The invention provides a compound represented by the formula (I): (wherein E represents a 5- or 6-membered aromatic ring which may have a substituent or the like, W represents –NR-CO- (R represents a lower alkyl group) or the like, X represents –NR2-COR1 (R1 represents a lower alkyl group or the like and R2 represents a hydrogen atom or the like), and Y represents a hydrogen atom or the like) or a pharmaceutically acceptable salt thereof, which is useful for treatment of a disease such as convulsion, acute pain, inflammatory pain, chronic pain, gastrointestinal disorder, brain disorder such as cerebral infarction or transient cerebral ischemic attack, mental dysfunction such as schizophrenia, anxiety or drug dependence because it has an action of inhibiting metabotropic glutamate receptor 1.
C07D 277/20 - Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 277/46 - Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
C07D 277/48 - Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
C07D 277/56 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
C07D 417/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
52.
NPY Y4 AGONIST AS THERAPEUTIC AGENT FOR DISEASE ACCOMPANIED BY INTESTINAL TRACT DYSFUNCTION
Disclosed is an agent capable of ameliorating the intestinal tract dysfunction through a novel action mechanism. Also disclosed is a method for the evaluation of a compound, including the screening of the agent. A disease accompanied by intestinal tract dysfunction can be ameliorated or treated by using an NPY Y4 agonist as a therapeutic agent. A compound capable of ameliorating or treating a disease accompanied by intestinal tract dysfunction can be evaluated or screened by evaluating a compound targeting to an NPY Y4 receptor.
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 1/15 - Fungi ; Culture media therefor modified by introduction of foreign genetic material
C12N 1/19 - Yeasts; Culture media therefor modified by introduction of foreign genetic material
C12N 1/21 - Bacteria; Culture media therefor modified by introduction of foreign genetic material
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
It is found that &bgr;-catenin is a substrate for PLK1 and the phosphorylation site in &bgr;-catenin is Ser-718. Therefore, by using &bgr;-catenin or a peptide containing Ser-718 in &bgr;-catenin as a substrate, it becomes possible to achieve an evaluation or the like (e.g., screening) of a compound useful as a drug that targets PLK1.
C12N 15/00 - Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
Disclosed is a compound represented by the formula (I) below or a pharmaceutically acceptable salt thereof. ⏧In the formula, X, Y, Z and W independently represent a methine group or a nitrogen atom, but all X, Y, Z and W are not methine groups at the same time; A represents -O- or the like; B represents -C(O)- or the like; D represents -(CH2)m2-, -O- or the like, and m2 represents 0 or 1; Q represents a methine group or a nitrogen atom; and R represents a group represented by the following formula (II-1): (Wherein R6, R7 and R8 independently represent a lower alkyl group or the like).]
C07D 491/107 - Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
A61K 31/4355 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/02 - Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Disclosed is a compound represented by the formula (I) below and a pharmaceutically acceptable salt thereof. This compound is useful for treatment of obesity, diabetes and the like. ⏧In the formula (I), Ar represents a benzene ring or the like; X1 represents a nitrogen atom, a sulfur atom or the like; R1 represents an aryl group or the like; X2 represents a group represented by the following formula (II): (wherein R4 and R5 respectively represent a lower alkyl group or the like, and m represents a number of 2-4) or the like; one of X and Y represents an oxygen atom and the other represents a sulfanyl group or the like; and X3-X6 respectively represent -CH-, a nitrogen atom or the like.]
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 31/4365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
A61K 31/4535 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 411/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 411/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Disclosed is a compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: wherein R1 represents a heteroaryl group which may have a substituent or the like; R2 represents a lower alkyl group; R3 represents a heteroaryl group which has at least one nitrogen atom and may have a substituent or the like; X1 represents a carbon or nitrogen atom; ; X2 represents a carbon or nitrogen atom; and X3 represents a carbon or sulfur atom. The compound or the salt has an inhibitory effect on a metabotropic glutamate receptor 1, and therefore is useful for the treatment of a disease such as convulsion, acute pain, inflammatory pain, chronic pain, a gastrointestinal disorder, a brain disorder (e.g., cerebral infarction, transient cerebral ischemic attack), a mental dysfunction (e.g., schizophrenia), anxiety and drug dependence.
C07D 277/20 - Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/04 - Centrally acting analgesics, e.g. opioids
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
57.
METHOD FOR EVALUATION OF COMPOUND CAPABLE OF ACTING ON PLK3
It is found that topoisomerase II&agr; is a substrate for PLK3 and the phospholylated site in topoisomerase II&agr; corresponds to Thr at position 1342. Based on the finding, the evaluation (e.g., screening) of a compound for use as a therapeutic agent targeted to PlK3 becomes possible by using topoisomerase II&agr; or a substrate having the phospholylated site therein as a substrate. It is also found that the morphological change of a cancer cell having activated Ras is observed when PLK3 is over-expressed or activated. Based on the finding, a method for evaluation of a PLK3 activator and the PLK3 activator are provided.
Disclosed is an aryl-substituted nitrogen-containing heterocyclic compound represented by the formula (I) below or a pharmaceutically acceptable salt thereof. This compound serves as a nociceptin receptor antagonist and is useful as a pharmaceutical agent for treating diseases associated with a nociceptin receptor. (I) ⏧In the formula, A1, A2 and A3 independently represent a carbon atom or a nitrogen atom, and one or two of A1, A2 and A3 represent a carbon atom; R1 represents a lower alkyl group or the like; R2 represents a phenyl group which may be substituted by a halogen atom or the like; R3 represents a hydrogen atom, a lower alkyl group or the like; and R4 represents a lower alkyl group or the like.]
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/417 - Imidazole-alkylamines, e.g. histamine, phentolamine
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Disclosed is a compound represented by the formula (I) below, which has a glucokinase-activating effect and is thus useful for treatment of diabetes or obesity, or a pharmaceutically acceptable salt thereof. ⏧In the formula, R1 represents an aryl or the like; R11 represents an aryl or the like; R2 represents a formyl or the like; R3 represents a C1-6 alkyl or the like; R4 represents a hydrogen atom or the like; Z1 represents -O- or the like; Z2 represents -O- or the like; Y1-Y4 respectively represent a carbon atom or a nitrogen atom; ring A represents a heteroaryl group; X represents a carbon atom or the like; m represents an integer of 0-2; and q represents an integer of 0-2.]
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Disclosed are: novel use of an agonist of histamine receptor H3 protein (e.g., Imetit) for the prevention of obesity or the reduction of food intake; a method for evaluation of a compound for use as a therapeutic agent targeted to histamine receptor H3 protein; and a compound provided by the method.
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61K 31/417 - Imidazole-alkylamines, e.g. histamine, phentolamine
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
A method of detecting a reactive metabolite which involves the reaction step wherein a metabolic reaction of a test compound is conducted in the presence of two labeled nucleophiles and the detection step wherein the label of the nucleophile bonded to the reactive metabolite is detected; and a method of detecting a reactive metabolite which further involves the separation step wherein a liquid layer separation is conducted by using ammonium acetate to give an organic layer after the completion of the reaction step as described above. Use of these detection methods makes it possible to quantitatively detect a reactive metabolite while using convenient preparation procedures. Moreover, it becomes possible thereby to avoid the formation of false positive signals and lessen the formation of false negative signals. As a result, a test compound can be more accurately and more efficiently screened.
C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups
G01N 33/60 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances involving radioactive labelled substances
G21H 5/02 - Applications of radiation from radioactive sources or arrangements therefor, not otherwise provided for as tracers
Disclosed is a compound represented by the formula (I): wherein R1 and R2 independently represent a hydrogen atom, a lower alkyl group or the like; X1, X2 and X3 independently represent a methine group or a nitrogen atom; Y1 and Y3 independently represent a single bond, -O- or the like; Y2 represents a lower alkylene group or the like; W1 to W4 independently represent a single bond, a methlene group or the like; L represents a single bond, a methylene group or the like; Z1 and Z2 independently represent a single bond, a C1-4 alkylene group or the like; Ar1 represents an aromatic carbocyclic ring or the like; and Ar2 represents a bicyclic aromatic carbocyclic ring or the like. The compound is useful as a pharmaceutical for a central disease, a cardiovascular disease or a metabolic disease.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A compound represented by the formula (I) is contained as an active ingredient: wherein R1 and R2 independently represent a hydrogen atom, a lower alkyl group or the like, or R1 together with a nitrogen atom to which L, Z2 and R1 are attached may form an aliphatic nitrogenated heterocyclic group and R1 and R2 together with a nitrogen atom to which they are attached may form an aliphatic nitrogenated heterocyclic group; X represents a methine group or a nitrogen atom; Y represents -CH2-O-, -CH=CH- or the like; Z1 represents a single bond, a C1-4 alkylene group or the like; Z2 represents a single bond or a C1-4 alkylene group; L represents a methylene group, a C3-8 cycloalkylene group or the like; and Ar represents an aromatic carbocyclic group or the like. The compound is useful as a pharmaceutical for a central nerves system disease, a cardiovascular disease or a metabolic disease.
C07D 213/64 - One oxygen atom attached in position 2 or 6
A61K 31/4412 - Non-condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 7/08 - Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
A61P 15/06 - Antiabortive agents; Labour repressants
A61P 15/08 - Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
A61P 15/10 - Drugs for genital or sexual disorders; Contraceptives for impotence
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 413/10 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
An active ingredient is a compound represented by the general formula ⏧I]: ⏧I] ⏧wherein R1 and R2 represent a lower alkyl group, a C3-8 cycloalkyl group or the like, X1 and X2 represent methine, an Ar-Y1-Y2-Y3-substituted methine or the like, however, either of them is an Ar-Y1-Y2-Y3-substituted methine, X3 to X8 represent methine, -N- or the like, Y1 and Y3 represent a single bond, -O- or the like, Y2 represents a single bond, a lower alkylene group or the like, W represents -(O)-(CH2)n-(O)- or the like, n represents an integer of 1 to 4, L and Z2 represent a single bond or a methylene group, Z1 represents a single bond, a C1-4 alkylene group or the like, and Ar represents an aromatic carbocyclic group or the like]. The compound acts as a melanin-concentrating hormone receptor antagonist and is useful as a therapeutic agent for obesity or the like.
C07D 213/64 - One oxygen atom attached in position 2 or 6
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61K 31/4412 - Non-condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
A61K 31/4418 - Non-condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 7/08 - Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07D 239/46 - Two or more oxygen, sulfur or nitrogen atoms
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
It is intended to provide a molecule which is present on the Rb pathway and can be used as a drug discovery target for an anticancer agent or a tumor marker and a method capable of evaluating a compound (a candidate compound for an anticancer agent) using the molecule. The object can be achieved by a method for evaluating a compound which detects the interaction between IL-8, IL-8 receptor, ECT2, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, CCNE2, FEN1, HMGB2, CENPE, KIF20A, CDC25C, CDCA8, KIF11, HCAP-E, HCAP-G, KNTC2, HCAP-C, BUB1, NEK2, CCNA2 or KIF18A gene or protein and a test compound.
The present invention relates to a process for producing crystalline trans-N-⏧l-(2-fluorophenyl)- S-pyrazoly]-3-oxospiro⏧6-azaisobenzofuran-1(3H),1'-cyclohexane]-4'-carboxamide and novel salts, hydrates and polymorphs thereof.
A61K 31/4355 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having oxygen as a ring hetero atom
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
67.
SPIROCHROMANONE DERIVATIVES AS ACETYL COENZYME A CARBOXYLASE (ACC) INHIBITORS
The invention relates to a compound of a formula (I): , or a pharmaceutically acceptable salt or ester thereof, useful as a therapeutic agent for various ACC-related disorders.
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
The invention relates to a compound of a formula (I): or a pharmaceutically acceptable salt or ester thereof, useful as a therapeutic agent for various ACC-related disorders.
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A pharmaceutical comprising the combination of a diaryl-substituted 5-membered heterocyclic derivative having an mGluR1 inhibitory effect and one or more substances selected from the group consisting of (i) an mGluR1 inhibitor other than the derivative, (ii) an anticonvulsant, (iii) a therapeutic agent for an acute pain, an inflammatory pain or a chronic pain, (iv) a therapeutic agent for a brain disorder such as cerebral infarction or transient ischemic attach, (v) a therapeutic agent for schizophrenia, (vi) an antianxiety agent, (vii) a therapeutic agent for drug dependence, (viii) a therapeutic agent for Parkinson's disease and (ix) a therapeutic agent for a gastrointestinal disorder.
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 25/00 - Drugs for disorders of the nervous system
A61P 43/00 - Drugs for specific purposes, not provided for in groups
It is intended to provide a compound represented by the formula (I) (I) (wherein R represents an alkyl group having 1 to 6 carbon atoms substituted with 2 hydroxyl groups, Cy represents a bicyclic or tricyclic aliphatic carbocyclic group having 6 to 10 carbon atoms which may have a substituent in some cases). The compound acts as a nociceptin receptor antagonist and is useful as, for example, a narcotic analgesic resistance reversal agent; a reversal agent for narcotic analgesic dependency or withdrawal syndrome; an analgesic action enhancing agent; an anti-obesity agent or an appetite control agent; an improving agent or preventive agent for decline in learning and memory abilities or dementia symptom; an improving agent for cognitive function in the developmental stage; a therapeutic agent for schizophrenia; a therapeutic agent for regressive neurodegenerative disease; an antidepressant agent or an emotion control agent; a therapeutic agent or preventive agent for diabetes insipidus; a therapeutic agent or preventive agent for polyuria; a therapeutic agent for hypopiesis and the like.
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/02 - Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 13/02 - Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 19/06 - Antigout agents, e.g. antihyperuricemic or uricosuric agents
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
A61P 43/00 - Drugs for specific purposes, not provided for in groups
A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein X1 to X4 independently represent a carbon atom or the like; the ring A represents a 5- to 6-membered heteroaryl having 1 to 4 heteroatoms independently selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom; X5 represents an oxygen atom or the like; X represents a carbon atom or the like; Het represents a 5- or 6-membered aliphatic heterocycle; R1 represents an aryl or the like; R2 represents a formyl group or the like; and R3 represents a -C1-6 alkyl or the like. The compound or salt has a glucokinase activation effect and is useful as a therapeutic agent for diabetes.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
72.
METHOD FOR PRODUCING 4(3H)-QUINAZOLINONE DERIVATIVE
Disclosed is a method for producing 2-methyl-3-4- ⏧3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone comprising a step for reacting 2-methyl-5-trifluoromethyl-4H-3,1-benzoxazine-4-one with 4-⏧3-(1-pirrolidinyl)propoxy]aniline or an acid addition salt thereof, or 4-(1-cyclobutyl-4-piperidinyl)oxyaniline or an acid addition salt thereof in the presence of an acetic acid catalyst.
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
A method for evaluation of a compound comprising the steps of introducing an RSK1 gene into a cell to prepare a cell capable of expressing RSK1, contacting a compound to be evaluated with the cell, and detecting the specific binding of the compound to RSK1; and a compound given by the method. The compound can be used as a potentiator of cisplatin. The method enables to find a gene which acts specifically on a cell of cancer induced by the abnormality in p53 or enhanced MAPK pathway and to evaluate a compound by using the gene.
An NPY Y2 agonist is used as a therapeutic agent for a disease accompanied by diarrhea. A compound capable of treating the disease can be evaluated and screened by examining the compound on the targeting to an NPY Y2 receptor. An agent capable of inhibiting the diarrhea by a novel mechanism of action; and a method for evaluation of a compound, including the screening for the agent.
Disclosed is a process for producing a 4(3H)-quinazolinone derivative, which is useful as a medicinal substance, with better efficiency in an industrial scale. The process comprises the steps of reacting 4-hydroxy-N-tert-butoxycarbonylpiperidine with 4-fluoro-1-nitrobenzene in the presence of sodium hydride, reacting the resulting product with cyclobutanone, reducing the resulting product to give 4-(1-cyclobutyl- 4-piperidinyl)oxyaniline, and reacting this compound with 2-methyl-5-trifluoromethyl-4H-3,1-benzoxadin-4-one to give 3-⏧4-⏧(1-cyclobutyl-4-piperidinyl)oxy]phenyl]- 2-methyl- 5-trifluoromethyl-4(3H)-quinazolinone.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
76.
NOVEL AMINOPYRIDINE DERIVATIVE HAVING SELECTIVE AURORA-A INHIBITORY ACTIVITY
A compound represented by the general formula ⏧I]: (I) ⏧wherein m1 and m2 each is 1, 2, or 3; n1 and n2 each is 0 or 1; i is an integer of 1 to m1; j is an integer of 1 to m2; R is optionally substituted aryl, heteroaryl, or cycloalkyl; Rai and Rai' each is hydrogen, etc.; Rbj and Rbj' each is hydrogen, etc.; Rc, Rd, and Re each is hydrogen, etc.; X1 is CH, CX1a, or N; X2 is CH, N, etc.; X3 is CH, N, etc.; X4 is CH or N; Y1, Y2, and Y3 are the same or different and each is CH or N; Z1 and Z2 are the same or different and each is CH or N; and W is a 5-membered aromatic heterocycle, e.g., pyrazole or thiazole] or a pharmaceutically acceptable salt or ester of the compound; and a selective Aurora-A inhibitor or anticancer agent each containing the compound, salt, or ester. Also provided is a use of the anticancer agent in combination with other anticancer agent.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/337 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 403/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
Disclosed is a substance having an antagonistic effect on the binding of histamine to a histamine H3 receptor or an inhibitory effect on the activity which a histamine H3 receptor constantly exhibits. A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein R1 represents a phenyl group which may be substituted or the like and R2 represents a cyano group which may be substituted or the like, or R1 and R2 together form an aliphatic hetetocyclic ring which may be substituted; R3 represents a group represented by the formula (II-1) below; and all of X1 to X4 represent a carbon atom or the like: (II-1) where R4 and R5 represent a lower alkyl group or the like; and m1 represents an integer of 2 to 4.
C07D 211/22 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulfur atoms by oxygen atoms
A61K 31/438 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring being spiro-condensed with carbocyclic or heterocyclic ring systems
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 5/48 - Drugs for disorders of the endocrine system of the pancreatic hormones
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 43/00 - Drugs for specific purposes, not provided for in groups
C07D 211/32 - Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
C07D 211/52 - Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
C07D 211/62 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
It is intended to provide a method for evaluating a compound which regulates eating or body weight characterized by comprising the steps of introducing a BARLP gene and preparing a cell expressing BARLP; bringing a test compound into contact with the cell; and detecting a specific binding of the test compound to the BARLP and a method for evaluating a compound further comprising the step of evaluating a test compound using a nonhuman genetically-engineered animal in which the BARLP gene is inactivated. According to this invention, knowledge about a relationship between BARLP and biological functions is obtained and a method for evaluating a compound targeting BARLP and a BARLP ligand obtained by the evaluation can be provided.
A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein R1 represents a branched alkyl group having 3 to 9 carbon atoms or the like; R2 represents a 6-membered heteroaryl group having 1 or 2 nitrogen atoms or the like; R3 represents a hydrogen atom, an alkanoylamino group or the like; R4 represents a hydrogen atom, a lower alkyl group or the like; X1 represents an oxygen or sulfur atom; X2 represents an oxygen atom or a single bond; and m is an integer of 0 to 4. This compound has a metabotropic glutamate receptor 1 inhibitory effect, and therefore is useful for the treatment of a brain disorder such as convulsion, acute pain, inflammatory pain, chronic pain, cerebral infraction or transient cerebral ischemic attack, a mental dysfunction such as schizophrenia, and a disease such as anxiety and drug addiction.
C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/04 - Centrally acting analgesics, e.g. opioids
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence
C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
C07D 263/58 - Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
C07D 277/20 - Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
C07D 277/42 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 417/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
80.
METHOD OF MEASURING ENZYME ACTIVITY AND METHOD OF EVALUATING COMPOUND
It is intended to provide a method of measuring an activity, which is a method of measuring an activity of an enzymatic reaction in which a lipid-soluble reaction product is formed by catalyzing an addition reaction of two or more kinds of substrates, characterized by comprising a labeling step in which any one of the substrates is labeled, a reaction step in which an enzymatic reaction is carried out in the presence of an enzyme, all substrates and an acceptor, and a detection step in which the reaction product is detected by bringing the labeled molecule and a molecule to be detected close to each other via the acceptor and transferring an energy generated by the labeled molecule to the molecule to be detected, and a method of evaluating a compound utilizing the method of measuring an activity. By the methods of the invention, it is possible to perform a treatment from the enzymatic reaction to the measurement of an enzyme activity with the simple steps and it is possible to provide a method of measuring an enzyme activity which can be applied to an HTS evaluation system.
C12Q 1/25 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving enzymes not classifiable in groups
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
C12Q 1/527 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving lyase
G01N 37/00 - INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES - Details not covered by any other group of this subclass
81.
THERAPEUTIC AGENT FOR NON-ALCOHOLIC FATTY LIVER DISEASE, AND SCREENING METHOD FOR DRUG CANDIDATE COMPOUND FOR TREATMENT OR PREVENTION OF NON-ALCOHOLIC FATTY LIVER DISEASE
A therapeutic agent for a non-alcoholic fatty liver disease comprising a melanin-concentrating hormone receptor antagonist as an active ingredient, which is developed based on a novel mechanism of action that a melanin-concentrating hormone receptor is involved in non-alcoholic fatty liver diseases. A method for screening a drug candidate compound for the treatment or prevention of a non-alcoholic fatty liver disease by utilizing the mechanism.
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 43/00 - Drugs for specific purposes, not provided for in groups
⏧PROBLEMS] To obtain a non-human transgenic mouse that can be used for inducing in vivo expression of a nucleic acid molecule and/or a protein that is not expressed sufficiently when it is induced by a drug substance; and to provide a method for producing the same. ⏧MEANS FOR SOLVING PROBLEMS] With the method for producing a non-human transgenic animal characterized by comprising the steps of producing a TetR gene introduced cell by introducing an expression vector in which TetR gene is located downstream of a promoter into a fertilized egg or an embryonic stem cell; and obtaining a TetR gene introduced non-human transgenic animal by introducing the TetR gene introduced cell into a non-human mammal and the non-human transgenic animal produced by the production method, it becomes possible to obtain a non-human transgenic animal that can be used when the expression of a nucleic acid molecule and/or a protein that is not expressed sufficiently when it is induced by a drug substance is induced in vivo.
A substance that has a potency antagonistic to coupling of histamine with histamine H3 receptor or a potency of inhibiting the constant activity of histamine H3 receptor. There is provided a form I crystal of 2-methyl-3-4-⏧3-(1-pyrrolidinyl)propoxy]phenyl}-5-trifluoromethyl-4(3H)-quinazolinone that in the powder X-ray diffractometry, has peaks at 6.4°, 9.7°, 10.2°, 12.9°, 14.2°, 14.7°, 16.0°, 16.3°, 16.8°, 17.6°, 19.5°, 20.3°, 20.6°, 21.2°, 21.8°, 22.1°, 22.4°, 22.6°, 24.0°, 24.3°, 24.9°, 25.7°, 25.9°, 26.5°, 26.7°, 27.4°, 29.1°, 29.4°, 32.3° and 39.0° diffraction angles (2&thetas;됙0.2°).
C07D 239/91 - Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
A61K 31/517 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 3/12 - Drugs for disorders of the metabolism for electrolyte homeostasis
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 25/30 - Drugs for disorders of the nervous system for treating abuse or dependence
Detection of p53 dysfunction or molecular diagnosis of cancer is carried out by a method comprising the steps of measuring the expression level of at least one gene selected from the group consisting of CARS, MOCOS, TNFRSF9, LOC56901 and GEF-H1 or a gene which is functionally equivalent to the gene in a test tissue or a test cell; comparing the expression level of the gene with that of a corresponding gene in a normal tissue or a normal cell; and determining whether or not the expression level of the gene in the test tissue or the test cell is significantly higher than that of the corresponding gene in the normal tissue or the normal cell based on the comparison result. According to the method for molecular diagnosis of the present invention, regardless of the presence of p53 mutation or without directly detecting p53 mutation, it becomes possible to detect p53 dysfunction or to diagnose cancer caused by p53 dysfunction.
G01N 37/00 - INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES - Details not covered by any other group of this subclass
patents
