Provided are a fused bicyclic heteroaryl amide compound as a protein aggregation inhibitor, as well as the use of such compound in the treatment or prevention of neurodegenerative diseases characterized by protein aggregation, such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, dementia with Lewy bodies, Parkinson's disease dementia, multiple system atrophy, amyotrophic lateral sclerosis, Huntington's disease, and cancer.
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
A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
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 31/454 - 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/519 - PyrimidinesHydrogenated 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
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
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
The present invention provides a crystal form or salt of a bicyclic heteroaryl amide compound, a preparation method therefor and a use thereof. Specifically, the present invention relates to a crystal form or salt of a compound of general formula (I) or a stereoisomer of said compound, a preparation method therefor and a use thereof in treating or preventing neurodegenerative diseases characterized by protein aggregation.
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 487/02 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains two hetero rings
C07D 495/02 - Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
C07D 247/00 - Heterocyclic compounds containing rings having two nitrogen atoms as the only ring hetero atoms, according to more than one of groups
C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
Provided is an RNAi agent for inhibiting the expression of apolipoprotein (a) gene (LPA) in a cell. The RNAi agent comprises a sense strand and an antisense strand which form a double-stranded region. The antisense strand has a length of no more than 23 nucleotides and comprises any nucleotide sequence selected from SEQ ID NOs: 265 to 528. Also provided is a use of the RNAi agent in treatment of cardiovascular and cerebrovascular diseases, etc.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
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 present invention relates to a cyclic amine derivative or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the cyclic amine derivative or the pharmaceutically acceptable salt thereof, and the use of the cyclic amine derivative or the pharmaceutically acceptable salt thereof or the composition thereof. The cyclic amine derivative of the present invention has a relatively strong capacity of binding to apo(a), can effectively reduce the level of Lp(a), and has low toxic side effects.
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 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
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
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
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 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
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
6.
LIGAND-OLIGONUCLEOTIDE CONJUGATE AND LINKER FOR CONJUGATE
A ligand-oligonucleotide conjugate and a linker for the conjugate, the linker including the structure of formula I or II: -NR1-C(O)-[C(R3R4nn-C(O)-[NR2-C(RaRbpp- (formula I), or -NR1-[C(O)-C(RaRb)-NR2pp-C(O)-[C(R3R4nn-C(O)- (formula II). Also provided are a preparation method for the conjugate, and an intermediate.
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
7.
FUSED BICYCLIC HETEROARYL AMIDE COMPOUND AS PROTEIN AGGREGATION INHIBITOR
Provided are a fused bicyclic heteroaryl amide compound as a protein aggregation inhibitor, as well as the use of such compound in the treatment or prevention of neurodegenerative diseases characterized by protein aggregation, such as Alzheimer's disease, Parkinson's disease, frontotemporal dementia, dementia with Lewy bodies, Parkinson's disease dementia, multiple system atrophy, amyotrophic lateral sclerosis, Huntington's disease, and cancer.
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 487/02 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains two hetero rings
C07D 495/02 - Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
C07D 247/00 - Heterocyclic compounds containing rings having two nitrogen atoms as the only ring hetero atoms, according to more than one of groups
C07D 241/04 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
A61K 31/4045 - Indole-alkylaminesAmides thereof, e.g. serotonin, melatonin
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
The present invention provides a maleate, phosphate, sulfate, hydrochloride of a cyclohexane derivative, N′-[trans-4-[2-[7-(benzo[b]thiophene)-7-piperazinyl]ethyl]cyclohexyl]-N,N-dimethylurea, as shown in Formula I and crystal forms thereof. The crystal forms have low hygroscopicity and good stability and are convenient for long-term storage and transportation; or the crystal forms have a long half-life in vivo, high bioavailability and small individual difference, and thus have obvious clinical application advantages.
C07D 333/66 - Nitrogen atoms not forming part of a nitro radical
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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
A blood coagulation factor XIa inhibitor of formula I, a pharmaceutical composition containing same, a preparation method therefor, and use thereof in preparation of drugs for prevention or treatment of thrombosis and embolism-related diseases.
C07D 257/06 - Five-membered rings with nitrogen atoms directly attached to the ring carbon atom
C07D 471/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups
C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
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 present invention provides a maleate, phosphate, sulfate, and hydrochloride of a cyclohexane derivative, N'-[trans-4-[2-[7-(benzo[b]thiophene)-7-piperazinyl]ethyl]cyclohexyl]-N,N-dimethylurea, as shown in formula I and crystal forms thereof. The crystal forms have low hygroscopicity and good stability and are convenient for long-term storage and transportation; or the crystal forms have a long half-life in vivo, high bioavailability, and small individual differences, and thus have obvious clinical application advantages.
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
The present invention provides a maleate, phosphate, sulfate, and hydrochloride of a cyclohexane derivative, N'-[trans-4-[2-[7-(benzo[b]thiophene)-7-piperazinyl]ethyl]cyclohexyl]-N,N-dimethylurea, as shown in formula I and crystal forms thereof. The crystal forms have low hygroscopicity and good stability and are convenient for long-term storage and transportation; or the crystal forms have a long half-life in vivo, high bioavailability, and small individual differences, and thus have obvious clinical application advantages.
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
The present invention provides a method for preparing a cyclohexane derivative, comprising the following steps: (1) subjecting a compound SM01 and a compound SM02 or a salt thereof to a nucleophilic substitution reaction to obtain a compound A; (2) deprotecting the compound A to obtain a compound B; and (3) subjecting the compound B and an acylation reagent to an acylation reaction to obtain a cyclohexane derivative. The method provided by the present invention has less side reactions, high product yield, and high product purity, and are suitable for industrial-scale production.
Provided is a method for preparing a cyclohexane derivative, the method comprising the following steps: subjecting a compound, 2-(4-(3,3-dimethylureido)cyclohexyl)acetaldehyde, represented by formula SM01 and a compound represented by formula SM02 to a condensation imine reduction reaction to obtain the cyclohexane derivative. The method of the present invention has few side reactions, a high product yield and a high product purity, and is favorable for the industrial scale production.
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
C07D 275/04 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
C07D 333/06 - Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulfur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
Disclosed are novel solid forms of 7-chloro-3-(5-dimethylaminomethyl-[1,2,4]oxadiazol-3-yl)-5-methyl-4,5-dihydro-imidazo[1,5-a][1,4]benzodiazepin-6-one, comprising crystalline form A, crystalline form B and an amorphous form. Also disclosed are preparation methods for the solid forms, and applications of the solid forms in the preparation of anxiolytics and/or anticonvulsants and/or non-sedative hypnotics.
A61K 31/5517 - 1,4-Benzodiazepines, e.g. diazepam condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
Disclosed are a stable oral pharmaceutical composition and a preparation method therefor. The composition contains an effective amount of a compound having the structure shown in formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, the pharmaceutically acceptable carrier comprising a polymer having a melting point, glass transition temperature and softening temperature of less than 180°C, the mass ratio of the polymer with respect to the compound having the structure shown in formula I or the pharmaceutically acceptable salt thereof being more than 1.
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
A61K 31/5517 - 1,4-Benzodiazepines, e.g. diazepam condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
2 receptors, and can be used as a therapeutic drug against neuropsychiatric diseases.
wherein; X is N or CH; R is
6 alkyl is optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br, and I.
C07C 275/26 - Derivatives of urea, i.e. compounds containing any of the groups the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of rings other than six-membered aromatic rings
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
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
C07D 261/20 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
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 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 275/04 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
17.
GENETICALLY ENGINEERED BACTERIUM OF COEXPRESSING CYCLOHEXANONE MONOOXYGENASE AND ISOPROPANOL DEHYDROGENASE AND USE THEREOF
The present invention provides a genetically engineered bacterium of coexpressing cyclohexanone monooxygenase and isopropanol dehydrogenase and use thereof, and the genetically engineered bacterium constructed can catalyze and convert high-concentration omeprazole sulfide into esomeprazole.
Crystal forms I and II of tasimelteon. Crystal form I: an X-ray powder diffraction spectrum using CuKα radiation and represented by a 2θ angle has diffraction peaks at least at 7.2º±0.2º, 7.9º±0.2º, 10.6º±0.2º, 14.4º±0.2º, 15.9º±0.2º, 17.3º±0.2º, 21.0º±0.2º, 23.2º±0.2º, and 24.4º±0.2º. Crystal form II: an X-ray powder diffraction spectrum using CuKα radiation and represented by a 2θ angle has diffraction peaks at least at 6.8º±0.2º, 12.1º±0.2º, 12.5º±0.2º, 13.1º±0.2º, 13.6º±0.2º, 13.8º±0.2º, 15.8º±0.2º, 17.0º±0.2º, 18.4º±0.2º, 20.8º±0.2º, 24.2º±0.2º, and 24.4º±0.2º. Crystal forms I and II of tasimelteon have advantages of excellent physicochemical property, good stability and solubility, and simple operation for preparation.
C07D 307/79 - Benzo [b] furansHydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
Provided are a cyclohexane derivative as shown by formula IB or a stereoisomer or a salt thereof, and the preparation and use thereof. The cyclohexane derivative has a high affinity for D3 receptors and 5-hydroxytryptamine, has a lower affinity for D2 receptors, shows a high selectivity for D3/D2 receptors, and can be used as a therapeutic drug against neuropsychiatric diseases wherein X is N or -CH-; where R group is optionally substituted with one or more substituents selected from halogen and Ci-Ce alkyl; and further where the Ci-Ce alkyl is optionally substituted with one or more substituents selected from the group consisting of F, Cl, Br and I.
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
C07D 333/66 - Nitrogen atoms not forming part of a nitro radical
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
A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
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
20.
CYCLOHEXANE DERIVATIVE OR STEREOISOMER OR SALT THEREOF, AND PREPARATION AND USE THEREOF
Provided are a cyclohexane derivative as shown by formula IB or a stereoisomer or a salt thereof, and the preparation and use thereof. The cyclohexane derivative has a high affinity for D3 receptors and 5-hydroxytryptamine, has a lower affinity for D2 receptors, shows a high selectivity for D3/D2 receptors, and can be used as a therapeutic drug against neuropsychiatric diseases; and the preparation method thereof is simple and easy.
C07D 333/54 - Benzo [b] thiophenesHydrogenated benzo [b] thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
C07D 333/66 - Nitrogen atoms not forming part of a nitro radical
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 413/04 - 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
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
A61P 25/18 - Antipsychotics, i.e. neurolepticsDrugs for mania or schizophrenia
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
The use of 7-chloro-3-(5-dimethylaminomethyl-[1,2,4]oxadiazol-3-yl)-5methyl-4,5-dihydro-imidazol[1,5,-a][1,4]benzodiazepine-6-one or its pharmaceutically acceptable salt for treating various types of insomnia.
A61K 31/5517 - 1,4-Benzodiazepines, e.g. diazepam condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam
01 - Chemical and biological materials for industrial, scientific and agricultural use
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Raw materials (for medicine). Pharmaceutical preparations; chemico-pharmaceutical
preparations; vitamin preparations; suppositories; medicines
for human purposes; preparations of trace elements for human
and animal use; injection; medicine (piece); medicinal
extract; traditional chinese medicines (prepared by a
pharmacy); medicinal gum; veterinary preparations; medicines
for veterinary purposes; chemical preparations for
veterinary purposes.
