Novel ionizable lipid compounds, compositions comprising such ionizable lipid compounds, and related methods of their use are disclosed. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including biologically active agents, such as siRNA or mRNA, are useful in the delivery of said biologically active agents to subjects in need thereof.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07C 227/18 - Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
C07C 229/12 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
C07D 233/90 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
2.
AN IMIDAZOLE-INDOLE DERIVATIVE BINDING TO 5-HT7 SEROTONIN RECEPTOR, A PHARMACEUTICAL COMPOSITION COMPRISING THE DERIVATIVE, USES OF THE DERIVATIVE AND THE COMPOSITION, AND AN INTERMEDIATE PRODUCT FOR MANUFACTURING THE IMIDAZOLE-INDOLE DERIVATIVE
INSTYTUT FARMAKOLOGII IM. JERZEGO MAJA PAN (Poland)
Inventor
Hogendorf, Adam
Szybiński, Marcin
Hogendorf, Agata
Moszczyński-Pętkowski, Rafał
Dubiel, Krzysztof
Mika, Joanna
Satała, Grzegorz
Bojarski, Andrzej J.
Matłoka, Mikołaj
Górka, Michał
Majkowska, Iwona
Abstract
The subject matter of the invention is an imidazole-indole derivative of Formula (I): wherein R1and R2131413133 alkylsulfanyl group, or R1and R2137777 serotonin receptor is involved in a subject. The subject matter of the invention is an intermediate product of Formula (II): wherein R1and R2 substituents are as defined above for the Formula (I).
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
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
3.
AN IMIDAZOLE-INDOLE DERIVATIVE BINDING TO 5-HT7 SEROTONIN RECEPTOR, A PHARMACEUTICAL COMPOSITION COMPRISING THE DERIVATIVE, USES OF THE DERIVATIVE AND THE COMPOSITION, AND AN INTERMEDIATE PRODUCT FOR MANUFACTURING THE IMIDAZOLE-INDOLE DERIVATIVE
INSTYTUT FARMAKOLOGII IM. JERZEGO MAJA PAN (Poland)
Inventor
Hogendorf, Adam
Szybinski, Marcin
Hogendorf, Agata
Moszczynski-Petkowski, Rafal
Dubiel, Krzysztof
Mika, Joanna
Satala, Grzegorz
Bojarski, Andrzej J.
Matloka, Mikolaj
Gorka, Michal
Majkowska, Iwona
Abstract
The subject matter of the invention is an imidazole-indole derivative of Formula (I): wherein R1 and R2 represent, independently of each other, a hydrogen atom, a halogen atom, a hydroxy group, a substituted or unsubstituted C1-C3 alkoxy group, a substituted or unsubstituted C1-C4 alkyl group, a C1-C3 alkylsulfonyl group, an amide group or a halo-C1-C3 alkylsulfanyl group, or R1 and R2 together form a C1-C3 alkylenedioxy group, or its pharmaceutically acceptable salt. The subject matter of the invention is also a pharmaceutical composition comprising an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt as an active substance. The subject matter of the invention is an imidazole-indole derivative of Formula (I) or its pharmaceutically acceptable salt or a pharmaceutical composition comprising an imidazole- indole derivative of Formula (I) or its pharmaceutically acceptable salt, for use as a 5-HT7 serotonin receptor agonist or for use as a medicine, in particular in the treatment and/or prevention of a disease or disorder in which 5-HT7 serotonin receptor is involved. Moreover, the subject matter of the invention is a method for the treatment or prevention of a disease or disorder in which 5-HT7 serotonin receptor is involved in a subject. The subject matter of the invention is an intermediate product of Formula (II): wherein R1 and R2 substituents are as defined above for the Formula (I).
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
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
4.
HUMAN FIBROBLAST GROWTH FACTOR 1 (FGF-1) MUTEINS, THEIR DIMERS AND USES
The present invention relates to human fibroblast growth factor (FGF-1) muteins having decreased mitogenicity, dimers of human FGF-1 muteins, as well as such human FGF-1 muteins and dimers of such muteins for use in reducing blood glucose level, particularly for use in the treatment of diabetes.
A61P 35/04 - Antineoplastic agents specific for metastasis
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
6.
BISPECIFIC ANTI-AXL AND ANTI-PD-L1 ANTIBODIES AND THEIR USE IN THERAPY, PARTICULARLY IN THE TREATMENT OF NEOPLASM
The present invention provides a bispecific antibody comprising one or more antigen-binding domains binding specifically to AXL antigen, and one or more antigen- binding domains binding specifically to PD-L1 antigen, the binding of which to AXL and/or PD-L1 antigen leads to its internalisation, as well as an antigen-binding fragment thereof binding specifically to AXL and/or PD-L1. The present invention provides also a nucleic acid encoding such a bispecific antibody, or antigen-binding fragment thereof, an antibody-drug conjugate comprising such a bispecific antibody, or antigen-binding fragment thereof, and a pharmaceutical composition comprising such a bispecific antibody, or antigen-binding fragment thereof, or such an antibody-drug conjugate, and a pharmaceutically acceptable excipient or carrier. Further, the present invention provides such a bispecific antibody or such a conjugate or such a pharmaceutical composition for use in therapy, for use in the therapy of a neoplasm, in particular a malignant neoplasm, particularly a neoplasm exhibiting surface expression of AXL and/or PD-L1. The invention provides also a method of treating or preventing neoplasm or its metastasis in an individual and a method of stimulating an immune response, comprising administering such a bispecific antibody, fragment, conjugate or pharmaceutical composition to the individual.
A61P 35/04 - Antineoplastic agents specific for metastasis
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
C07C 229/18 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to carbon atoms of six-membered aromatic rings
C07D 233/90 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 233/96 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
8.
NOVEL IONIZABLE LIPID COMPOUNDS FOR NUCLEIC ACID DELIVERY
Novel ionizable lipid compounds, compositions comprising such ionizable lipid compounds, and related methods of their use are disclosed. Nanoparticle compositions include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Nanoparticle compositions further including biologically active agents, such as siRNA or mRNA, are useful in the delivery of said biologically active agents to subjects in need thereof.
C07C 229/18 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to carbon atoms of six-membered aromatic rings
C07D 233/90 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07C 229/16 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
C07D 233/96 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
9.
HUMAN FIBROBLAST GROWTH FACTOR 1 (FGF-1) MUTEINS, THEIR DIMERS AND USES
The present invention relates to human fibroblast growth factor (FGF-1) muteins having decreased mitogenicity, dimers of human FGF-1 muteins, as well as such human FGF-1 muteins and dimers of such muteins for use in reducing blood glucose level, particularly for use in the treatment of diabetes.
The present invention relates to human fibroblast growth factor (FGF-1) muteins having decreased mitogenicity, dimers of human FGF-1 muteins, as well as such human FGF-1 muteins and dimers of such muteins for use in reducing blood glucose level, particularly for use in the treatment of diabetes.
The present invention relates to human fibroblast growth factor (FGF-1) muteins having decreased mitogenicity, dimers of human FGF-1 muteins, as well as such human FGF-1 muteins and dimers of such muteins for use in reducing blood glucose level, particularly for use in the treatment of diabetes.
An inhaler (400) for electronically supervised parenteral administration of a dry powder pharmaceutical composition comprising: storage means (410) for the pharmaceutical composition in a form of a dry powder; administration means (411) for ad- ministration of the pharmaceutical composition; memory (404) and processing means (402); communication means (401); controlled blocking means (403) for blocking administration of the pharmaceutical composition, wherein the inhaler (400) is adapted to receive data corresponding to an administration scheme (11), to determine whether a mobile device (300) with an authorisation token assigned thereto is present, and to control the controlled blocking means (403) so as to allow administration of the pharmaceutical composition only with compliance with the administration scheme (11) in the presence of the mobile device (300) with the authorisation token (12) assigned thereto.
A61K 31/137 - Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine
A61K 9/00 - Medicinal preparations characterised by special physical form
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
13.
Electronically Supervised Administration of a Pharmaceutical Composition
A system for electronically supervised administration of a pharmaceutical composition, that comprises an authorised entity node (100, 200) for an authorised entity, a mobile device (300) of a patient, and a medical device (400) adapted to administer the pharmaceutical composition, wherein the authorised entity node (100, 200) is adapted, when operated by the authorised entity, to generate data corresponding to an administration scheme (11) and an authorisation token (12) for assigning to a patient's mobile device (300), and to send the data corresponding to an administration scheme (11) and authorisation token (12) to the patient's mobile device (300). The mobile device (300) is adapted to send to the authorised entity node (100, 200) the data corresponding to the mobile device (300) and medical device (400), and to receive the authorisation token (12) assigned to a patient's mobile device (300) and send to the medical device (400) the data corresponding to the administration scheme (11) in response to receiving the authorisation token (12) assigned to a patients mobile device (300). The medical device (400) is provided with a controlled blocking means (403) for blocking administration of the pharmaceutical composition, is adapted to determine whether the mobile device (300) with the authorisation token assigned thereto is present and is adapted to control the controlled blocking means (403) so as to allow administration of the pharmaceutical composition only with compliance with the administration scheme (11) received from the mobile device (300) in the presence of the mobile device (300) with the authorisation token (12) assigned thereto.
G16H 20/13 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered from dispensers
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
A compound of the formula (I) wherein R represents a straight or branched, primary or secondary acyclic hydrocarbyl C3-C15 group, which can be saturated or unsaturated, or a straight or branched, primary or secondary acyclic hydrocarbyl C3-C15 group, which can be saturated or unsaturated and wherein one or more of hydrogen atoms is replaced with fluorine atom; X represents hydrogen atom or halogen atom, and * denotes chiral center, and salts thereof. The compound is useful for the treatment of diseases mediated by GPR40, in particular type II diabetes. (I)
C07C 59/68 - Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
15.
ELECTRONICALLY SUPERVISED ADMINISTRATION OF A PHARMACEUTICAL COMPOSITION
A system for electronically supervised administration of a pharmaceutical composition, that comprises an authorised entity node (100, 200) for an authorised entity, a mobile device (300) of a patient, and a medical device (400) adapted to administer the pharmaceutical composition, wherein the authorised entity node (100, 200) is adapted, when operated by the authorised entity, to generate data corresponding to an administration scheme (11) and an authorisation token (12) for assigning to a patient's mobile device (300), and to send the data corresponding to an administration scheme (11) and authorisation token (12) to the patient's mobile device (300). The mobile device (300) is adapted to send to the authorised entity node (100, 200) the data corresponding to the mobile device (300) and medical device (400), and to receive the authorisation token (12) assigned to a patient's mobile device (300) and send to the medical device (400) the data corresponding to the administration scheme (11) in response to receiving the authorisation token (12) assigned to a patient's mobile device (300). The medical device (400) is provided with a controlled blocking means (403) for blocking administration of the pharmaceutical composition, is adapted to determine whether the mobile device (300) with the authorisation token assigned thereto is present and is adapted to control the controlled blocking means (403) so as to allow administration of the pharmaceutical composition only with compliance with the administration scheme (11) received from the mobile device (300) in the presence of the mobile device (300) with the authorisation token (12) assigned thereto.
G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
G16H 20/17 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients delivered via infusion or injection
16.
AN INHALER FOR ELECTRONICALLY SUPERVISED PARENTERAL ADMINISTRATION OF A PHARMACEUTICAL COMPOSITION
An inhaler (400) for electronically supervised parenteral administration of a dry powder pharmaceutical composition comprising: storage means (410) for the pharmaceutical composition in a form of a dry powder; administration means (411) for administration of the pharmaceutical composition; memory (404) and processing means (402); communication means (401); controlled blocking means (403) for blocking administration of the pharmaceutical composition, wherein the inhaler (400) is adapted to receive data corresponding to an administration scheme (11), to determine whether a mobile device (300) with an authorisation token assigned thereto is present, and to control the controlled blocking means (403) so as to allow administration of the pharmaceutical composition only with compliance with the administration scheme (11) in the presence of the mobile device (300) with the authorisation token (12) assigned thereto.
2, halogen, alkyl C1-C4, alkoxyl C1-C3, and 6-membered heterocyclyl comprising 1 or 2 heteroatoms selected from the group consisting of N and O. The compound has the activity of kinase JAK1/JAK3 inhibitor and can find use in the treatment of chronic inflammatory and autoimmunological diseases.
An inhalable pharmaceutical composition comprising ketamine or its pharmaceutically acceptable salt for use in a method of treatment of depression by administration via pulmonary route, treatment comprising cycle of multiple sequences of administration by inhalation, said cycle lasting from 10 days to 30 days, wherein each of multiple sequences of administration is performed in a one single day, with 2 to 4 days intervals between sequences, and each of said sequences consists of multiple single dose inhalations separated by a break period lasting at least 5 minutes. The composition is especially useful for the treatment of treatment-resistant depression.
A compound of the formula (I)wherein R represents a straight or branched, primary or secondary acyclic hydrocarbyl C3–C15 group, which can be saturated or unsaturated, or a straight or branched, primary or secondary acyclic hydrocarbyl C3–C15 group, which can be saturated or unsaturated and wherein one or more of hydrogen atoms is replaced with fluorine atom; X represents hydrogen atom or halogen atom,and* denotes chiral center, and salts thereof. The compound is useful for the treatment of diseases mediated by GPR40, in particular type II diabetes. (I)
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
C07C 57/42 - Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings having unsaturation outside the rings
C07C 57/60 - Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen containing six-membered aromatic rings having unsaturation outside the rings
A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
20.
DRY POWDER KETAMINE COMPOSITION FOR USE IN THE TREATMENT OF DEPRESSION BY PULMONARY ADMINISTRATION
A dry powder inhalable pharmaceutical composition comprising ketamine or its pharmaceutically acceptable salt for use in a method of treatment of depression by administration via pulmonary route.The composition is especially useful for the treatment of treatment-resistant or treatment-refractory depression.
INSTYTUT FARMAKOLOGII POLSKIEJ AKADEMII NAUK (Poland)
Inventor
Kaminski, Krzysztof
Grychowska, Katarzyna
Canale, Vittorio
Bojarski, Andrzej J.
Satala, Grzegorz
Lenda, Tomasz
Popik, Piotr
Matloka, Mikolaj
Dubiel, Krzysztof
Moszczynski-Petkowski, Rafal
Pieczykolan, Jerzy
Wieczorek, Maciej
Zajdel, Pawel
Abstract
A compound of the formula (I) wherein R1represents hydrogen atom and R2represents moiety of the formula G1, or R1and R2333, naphthyl, quinolinyl, thienyl, thienyl substituted with halogen atom, and pyridyl; X is selected from the group consisting of -NR4, -0-, and -CHN(R522; R3is selected from the group consisting of hydrogen atom, methyl, ethyl, and cyclopropyl; R4is selected from the group consisting of hydrogen atom, straight or branched C1-C4 alkyl, straight or branched C1-C4 alkyl substituted with one or two halogen atoms, cyclopropyl and methylcyclopropyl; R5represents C1-C2 alkyl; k is an integer equal 1 or 2; I is an integer equal 1 or 2; m is an integer equal 0, 1 or 2; n is an integer 0 or 1 when X represents -NR4"or -CHN(R5) 2, wherein n is 1 only when m is 1; and n is 0 when X represents -0-; and acid addition salts thereof, can be useful as selective inhibitors of 5HT6 in the treatment of CNS diseases.
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 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 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 409/12 - 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 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
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
A compound or its acid addition salt of the general formula (I), wherein R1 represents phenyl substituted with one or two substituents selected from the group consisting of halogen and C1-C3 alkoxyl, or 6-membered heteroaryl with 1 or 2 nitrogen atoms, which is unsubstituted or substituted with a substituent selected from the group consisting of -NH2, halogen, alkyl C1-C4, alkoxyl C1-C3, and 6-membered heterocyclyl comprising 1 or 2 heteroatoms selected from the group consisting of N and O. The compound has the activity of kinase JAK1/JAK3 inhibitor and can find use in the treatment of chronic inflammatory and autoimmunological diseases.
A compound or its acid addition salt of the general formula (I), wherein R1 represents phenyl substituted with one or two substituents selected from the group consisting of halogen and C1-C3 alkoxyl, or 6-membered heteroaryl with 1 or 2 nitrogen atoms, which is unsubstituted or substituted with a substituent selected from the group consisting of -NH2, halogen, alkyl C1-C4, alkoxyl C1-C3, and 6-membered heterocyclyl comprising 1 or 2 heteroatoms selected from the group consisting of N and O. The compound has the activity of kinase JAK1/JAK3 inhibitor and can find use in the treatment of chronic inflammatory and autoimmunological diseases.
2, and their pharmaceutically acceptable salts. Pharmaceutical compositions comprising said compounds and their use in the treatment of diseases of immune system, inflammatory diseases and cancer.
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
A61K 31/554 - 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 sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
A61P 29/02 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
A61P 37/00 - Drugs for immunological or allergic disorders
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
25.
Fused triazole derivatives as phosphodiesterase 10A inhibitors
3), A represents unsubstituted or substituted 5-, 6- or 10-membered aryl or heteroaryl, n is 0 or 1 and B is a bicyclic heteromoiety defined in the specification. Compounds are phosphodiesterase 10A inhibitors and can find use in medicine in the treatment psychotic, neurological and cognitive functions diseases and disorders. (I)
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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
26.
7-(MORPHOLIN-4-YL)PYRAZOLE[1,5-A]PYRIMIDINE DERIVATIVES WHICH ARE USEFUL FOR THE TREATMENT OF IMMUNE OR INFLAMMATORY DISEASES OR CANCER
A compound of the general formula (I) wherein Y represents -CH2- or >C=0; R1 is selected from the group consisting of A1, A2 and A3; R2 represents dioxothiomorpholino moiety B1, piperazinyl moiety B2, azetidinyl moiety B3, or piperidinyl moiety B4; R3 is selected from the group consisting of H, halogen, and C1 -C4 alkyl; R4 is selected from the group consisting of C1 -C4 alkyl, C3-C4- cycloalkyl, C1 -C4 alkyl substituted with C1 -C4 alkoxy, and CHF2, and their pharmaceutically acceptable salts. Pharmaceutical compositions comprising said compounds and their use in the treatment of diseases of immune system, inflammatory diseases and cancer.
3 together with nitrogen atom to which they are both attached form a 6-membered saturated heterocyclic ring, wherein one of carbon atoms can be replaced with oxygen, —NH— or —N(C1-C2)alkyl-; and acid addition salts thereof. The compound can be useful in the treatment of cancer diseases. (I)
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 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 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 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
Disclosed are selected compounds of the general formula (I)Selected compounds exhibit phosphodiesterase 10A inhibitory activity. Also disclosed is the use of selected such compounds in the treatment of psychotic, neurological or cognitive function, disease or disorder.
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
31.
FUSED TRIAZOLE DERIVATIVES AS PHOSPHODIESTERASE 10A INHIBITORS
Compounds of the general formula (I), wherein one of X1 and X2 represents N, and the other one of X1 and X2 represents -C(CH3), A represents unsubstituted or substituted 5-, 6-or 10-membered aryl or heteroaryl, n is 0 or 1 and B is a bicyclic heteromoiety defined in the specification. Compounds are phosphodiesterase 10A inhibitors and can find use in medicine in the treatment psychotic, neurological and cognitive functions diseases and disorders. (I)
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
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61P 25/00 - Drugs for disorders of the nervous system
A compound of the general formula (I), useful for treating myeloproliferative, cancer,or inflammatory diseases, wherein Q represents a six-membered heteroaromatic ring containing 2 N atoms and R1 is hydrogen atom,or Q represents a five-membered heteroaromatic ring containing 1 or 2 heteroatoms selected from the group consisting of N and S,one substituent R1 is attached at C or N atom of said Q ringand R1 is selected from the group consisting of C1-C4-alkyl and C3-C4-cycloalkyl;R2 represents-NR7aR7bor-CH2-NR8aR8b;R3 represents C1-C4-alkyl;R4 represents phenylora 5-or 6-membered heteroarylcontaining 1 or 2 heteroatoms selected from the group consisting of N and S, and R4 is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of halogen, trifluoromethyl,hydroxyl and C1-C4-alkoxyl;R5 and R6 independently represent hydrogenatom or C1-C4-alkyl,and at least one of R5 and R6 represents hydrogen atom;and other substituents are as defined in the specification; and pharmaceutically acceptable salts thereof.
A compound represented by the general Formula (I), whereinhydrogen atoms shown as attached to pyrazole and benzimidazole rings are attached to one of nitrogen atoms of the pyrazole or benzimidazole ring, respectively; R1 represents -X-Q-P, wherein X is absent or represents CH2-, C(O)-, or C(O)NH-(CH2)k-, wherein k is 0, 1 or 2; Q is selected from the group consisting of Q1, Q2, Q3, Q4 and Q5; P is absent or represents straight-or branched-chain C1-C3 alkyl, (CH2)l-NR2R3, or(CH2)m-C(O)-NR2R3, wherein l and m independently of each other represent 0, 1 or 2, with the proviso that when B in Q1 represents oxygen atom, then P is absent;and R2and R3 independently represent C1 or C2 alkyl, or R2 and R3 together with nitrogen atom to which they are both attached form a 6- membered saturated heterocyclicring, wherein one of carbon atoms can be replaced with oxygen, -NH-or N(C1-C2)alkyl-; and acid addition salts thereof. The compound can be useful in the treatment of cancer diseases. (I)
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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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 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
A compound represented by the general Formula (I), whereinhydrogen atoms shown as attached to pyrazole and benzimidazole rings are attached to one of nitrogen atoms of the pyrazole or benzimidazole ring, respectively; R1 represents -X-Q-P, wherein X is absent or represents –CH2-, –C(O)-, or –C(O)NH-(CH2)k-, wherein k is 0, 1 or 2; Q is selected from the group consisting of Q1, Q2, Q3, Q4 and Q5; P is absent or represents straight-or branched-chain C1-C3 alkyl, –(CH2)l-NR2R3, or–(CH2)m-C(O)-NR2R3, wherein l and m independently of each other represent 0, 1 or 2, with the proviso that when B in Q1 represents oxygen atom, then P is absent;and R2and R3 independently represent C1 or C2 alkyl, or R2 and R3 together with nitrogen atom to which they are both attached form a 6- membered saturated heterocyclicring, wherein one of carbon atoms can be replaced with oxygen, -NH-or –N(C1-C2)alkyl-; and acid addition salts thereof. The compound can be useful in the treatment of cancer diseases. (I)
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 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
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
Pyrazolo[4,3-d]pyrimidin-7(6H)-one derivatives represented by the general formula (I), wherein R1 represents hydrogen atom or methyl; when R1 represents hydrogen atom, then R2 represents cyclopentyl, tetrahydropyranyl, cyclohexyl, or cyclohexyl substituted with 1 or 2 halogen atoms; when R1 represents methyl, then R2 represents cyclopentyl; R3 is selected from the group consisting of phenyl unsubstituted or substituted with 1 to 3 substituents selected from F, CI, Br, I, and OCH3; and 6- to 10-membered heteroaryl with 1 to 3 heteroatoms selected independently form O, N and S; and Q represents C1 -C3-alkylene group, which is unsubstituted or substituted with 1 to 3 C1 -C3-alkyl groups; and their salts. The compounds are PDE9A inhibitors useful as medicaments, in particular for treatment of cognitive function disorders and neurodegenerative diseases.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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
37.
IMIDAZO[1,2-B]PYRIDAZIN-6-AMINE DERIVATIVES AS KINASE JAK-2 INHIBITORS
A compound represented by the general formula (I) wherein R1represents H or C1-C4 alkyl; R2 represents phenyl substituted with one or two substituents selected from the group consisting of halogen atom and OC1-C4 alkyl;R3 represents phenyl or 5 to 10-membered monocyclic or bicyclic heteroaryl having from 1 to 4 ring heteroatoms selected from the group consisting of N, S, and O, which can be unsubstituted or substituted with a substituent selected from halogen atom, C1-C4-alkyl, and -C(O)O-C1-C4 -alkyl; and X represents –CH2-group or carbonyl-C(O)-group;and their acid addition salts;with the exclusion of 3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholinomethyl)-imidazo[1,2-b]pyridazine-6-amine and its salts. The compounds are JAK2 inhibitors and are useful as medicaments, especially for treating proliferative disorders and cancer diseases
A compound of the general formula (I) wherein R1 is selected from the group consisting of phenyl unsubstituted or substituted with 1 to 3 substituents selected from F, Cl, Br, I, CN, -O-C1-C3-alkyl, fluorinated -O-C1-C3-alkyl, -(CH2)mOH and 5-membered heterocyclic group with 1 or 2 heteroatoms selected from N, O and S; and 6- or 10-membered heteroaryl with 1 to 3 heteroatoms selected from O, N and S; R2 and R3 independently of each other represent H atom or straight or branched C1-C3 alkyl; R4 is selected from the group consisting of 4- to 6- membered cycloalkyl, wherein one of carbon atoms can be replaced by O atom, and which is unsubstituted or substituted with one or two halogen atoms,and straight or branched C1-C4 alkyl; Q represents a bond or C1-C3-alkylene, which can be optionally substituted by one to three C1-C3-alkyls; X is selected from the group consisting of O, NR5, and S(O)p; R5 represents H atom or C1-C3alkyl; m is 1, 2 or 3; p is 0, 1 or 2; and salts thereof, for use as a medicament, in particular for treating cognitive function disorders and neurodegenerative diseases.
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