Abstract

Disclosed are a heterocyclic compound, and an intermediate thereof, a preparation method therefor and the use thereof. Namely, provided are a heterocyclic compound as shown in formula I-a, and a tautomer and a pharmaceutically acceptable salt thereof, wherein the compound has a good water solubility and pharmacokinetic properties. Disclosed are a heterocyclic compound, and an intermediate thereof, a preparation method therefor and the use thereof. Namely, provided are a heterocyclic compound as shown in formula I-a, and a tautomer and a pharmaceutically acceptable salt thereof, wherein the compound has a good water solubility and pharmacokinetic properties.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Abstract

Disclosed in the present invention are a pharmaceutical composition, a preparation, and a preparation method therefor and the use thereof. The pharmaceutical composition contains an active ingredient and a pharmaceutically acceptable excipient. The active ingredient contains a compound represented by formula A. The compound represented by formula A is selected from one, two or more of the crystal form I, the crystal form III and the crystal form V. The excipient is selected-from or comprises, but is not limited to, one, two or more of the following excipients: a diluent, a disintegrant, an adhesive, a glidant and a lubricant. The pharmaceutical composition and the preparation of the present invention have a good safety and/or stability, and a high P2X3 antagonistic activity, and have less effect on the taste. Disclosed in the present invention are a pharmaceutical composition, a preparation, and a preparation method therefor and the use thereof. The pharmaceutical composition contains an active ingredient and a pharmaceutically acceptable excipient. The active ingredient contains a compound represented by formula A. The compound represented by formula A is selected from one, two or more of the crystal form I, the crystal form III and the crystal form V. The excipient is selected-from or comprises, but is not limited to, one, two or more of the following excipients: a diluent, a disintegrant, an adhesive, a glidant and a lubricant. The pharmaceutical composition and the preparation of the present invention have a good safety and/or stability, and a high P2X3 antagonistic activity, and have less effect on the taste.

IPC Classes  ?

• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61K 9/20 - Pills, lozenges or tablets
• A61K 9/28 - Dragees; Coated pills or tablets

Abstract

An acid addition salt of a ROCK inhibitor, and a crystal form, a composition and the pharmaceutical use thereof are provided. The acid addition salt is an acid addition salt of compound A and any one of the following acids: hydrochloric acid, p-toluenesulfonic acid, benzenesulfonic acid, maleic acid, tartaric acid, oxalic acid, fumaric acid, sulfuric acid, methanesulfonic acid, phosphoric acid, succinic acid or citric acid (A). The acid addition salt of compound A and the crystal form thereof have the characteristics of high solubility, good stability, high purity, few impurities and high bioequivalence, and are beneficial for the storage, quality control and druggability of drugs. An acid addition salt of a ROCK inhibitor, and a crystal form, a composition and the pharmaceutical use thereof are provided. The acid addition salt is an acid addition salt of compound A and any one of the following acids: hydrochloric acid, p-toluenesulfonic acid, benzenesulfonic acid, maleic acid, tartaric acid, oxalic acid, fumaric acid, sulfuric acid, methanesulfonic acid, phosphoric acid, succinic acid or citric acid (A). The acid addition salt of compound A and the crystal form thereof have the characteristics of high solubility, good stability, high purity, few impurities and high bioequivalence, and are beneficial for the storage, quality control and druggability of drugs.

IPC Classes  ?

• C07C 55/07 - Salts thereof
• A61K 31/10 - Sulfides; Sulfoxides; Sulfones
• A61K 31/194 - Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• C07C 51/43 - Separation; Purification; Stabilisation; Use of additives by change of the physical state, e.g. crystallisation
• C07C 57/145 - Maleic acid
• C07C 59/255 - Tartaric acid
• C07C 315/06 - Separation; Purification; Stabilisation; Use of additives
• C07C 317/14 - Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
• 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

Abstract

Disclosed are a crystal form of a heterocyclic compound, a preparation method therefor, and the use thereof. The heterocyclic compound is the compound represented by formula I. For the crystal form thereof, the X-ray powder diffraction pattern using Cu-Kα radiation and represented by 2θ angles has diffraction peaks at 8.95 ± 0.20°, 12.92 ± 0.20°, 16.39 ± 0.20°, 17.01 ± 0.20°, 17.44 ± 0.20°, 17.76 ± 0.20°, 18.08 ± 0.20°, 19.02 ± 0.20°, 21.95 ± 0.20°, 22.20 ± 0.20°, 23.49 ± 0.20°, 24.15 ± 0.20°, 24.92 ± 0.20°, 25.94 ± 0.20°, 27.14 ± 0.20° and 29.68 ± 0.20°. The crystal form of the heterocyclic compound has one or more of the following advantages: good chemical stability, good physical stability, promising patent medicine prospects and good preparation processability.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61P 25/18 - Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

Provided are a pharmaceutical composition comprising a heterocyclic compound, a preparation method therefor, and use thereof. Further provided is a pharmaceutical composition Q, comprising a substance X and a pharmaceutical excipient, the substance X being a compound represented by formula I, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of the pharmaceutically acceptable salt thereof. The pharmaceutical composition has one or more of the following advantages: the stability is good, the dissolution performance is good, the preparation method is simple, and the pharmaceutical composition is suitable for industrial production.

IPC Classes  ?

• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and 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
• A61P 25/18 - Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
• 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

Abstract

Disclosed by the invention is a heterocyclic compound, an intermediate, and a preparation method therefor and an application thereof. Provided by the invention are a heterocyclic compound as shown in formula I, and a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, a solvate, a metabolite, an ester, a pharmaceutically acceptable salt or a prodrug thereof. The heterocyclic compound has a high P2X3 antagonistic activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence. Disclosed by the invention is a heterocyclic compound, an intermediate, and a preparation method therefor and an application thereof. Provided by the invention are a heterocyclic compound as shown in formula I, and a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, a solvate, a metabolite, an ester, a pharmaceutically acceptable salt or a prodrug thereof. The heterocyclic compound has a high P2X3 antagonistic activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• C07D 413/06 - 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 only aliphatic carbon atoms
• 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
• C07F 5/04 - Esters of boric acids
• C07D 209/18 - 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 487/04 - Ortho-condensed systems
• A61P 11/14 - Antitussive agents

Abstract

Provided are a crystalline form of a compound represented by formula A, the crystalline form being crystalline form I, crystalline form II, crystalline form III, crystalline form IV, crystalline form V, crystalline form VI, crystalline form VII, crystalline form VIII or crystalline form IX, a preparation method therefor, a composition thereof, and an application thereof in the preparation of a P2X3 receptor antagonist or an application thereof in the preparation of drugs preventing and/or treating pains, urinary tract illness or respiratory system illness. The compound has high P2X3 antagonist activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence. Provided are a crystalline form of a compound represented by formula A, the crystalline form being crystalline form I, crystalline form II, crystalline form III, crystalline form IV, crystalline form V, crystalline form VI, crystalline form VII, crystalline form VIII or crystalline form IX, a preparation method therefor, a composition thereof, and an application thereof in the preparation of a P2X3 receptor antagonist or an application thereof in the preparation of drugs preventing and/or treating pains, urinary tract illness or respiratory system illness. The compound has high P2X3 antagonist activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems

Abstract

Disclosed is a heterocyclic compound as represented by formula (I), a tautomer thereof, or a pharmaceutically acceptable salt thereof. The compound has better inhibitory activity on TRPC5, has good metabolic stability in liver micro-particles, and has good clinical pharmacokinetic properties. Disclosed is a heterocyclic compound as represented by formula (I), a tautomer thereof, or a pharmaceutically acceptable salt thereof. The compound has better inhibitory activity on TRPC5, has good metabolic stability in liver micro-particles, and has good clinical pharmacokinetic properties.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed 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

Abstract

A ROCK inhibitor represented by formula (I), and a preparation method therefor and a use thereof are provided. The ROCK inhibitor has excellent ROCK inhibition activity, particularly shows good selective inhibition on ROCK2 kinase, has good safety and metabolic stability, and is high in bioavailability. The preparation method for the ROCK inhibitor is simple, and the ROCK inhibitor is easy to purify, and therefore has a good application prospect. A ROCK inhibitor represented by formula (I), and a preparation method therefor and a use thereof are provided. The ROCK inhibitor has excellent ROCK inhibition activity, particularly shows good selective inhibition on ROCK2 kinase, has good safety and metabolic stability, and is high in bioavailability. The preparation method for the ROCK inhibitor is simple, and the ROCK inhibitor is easy to purify, and therefore has a good application prospect.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• C07D 487/04 - Ortho-condensed systems
• 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 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 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 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

Abstract

Disclosed is a use of a heterocyclic compound. Specifically disclosed is a use of a heterocyclic compound in the preparation of a drug for treating and/or preventing respiratory diseases; the heterocyclic compound is a substance X, a tautomer thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or a solvate of the pharmaceutically acceptable salt thereof; the substance X is a compound as shown in formula I or a compound as shown in formula II; the heterocyclic compound of the present invention has a good cough relieving effect.

IPC Classes  ?

• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61K 31/352 - 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 condensed with carbocyclic rings, e.g. cannabinols, methantheline
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 11/14 - Antitussive agents

Abstract

The present invention relates to a compound having inhibitory activity for the lectin pathway of complement, a preparation method therefor, and an application thereof. Specifically, the present invention relates to a compound as represented by general formula (I'), a pharmaceutically acceptable salt thereof, a preparation method therefor, and an application thereof as a MASP-2 inhibitor, particularly an application in the preparation of a drug for treating diseases such as IgA nephropathy, TA-TMA, aHUS, and lupus nephritis.

IPC Classes  ?

• 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 493/04 - Ortho-condensed systems
• A61K 31/513 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• A61K 31/662 - Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 13/00 - Drugs for disorders of the urinary system

Abstract

A salt of a ROCK inhibitor, a crystal form of the salt, a composition, and a pharmaceutical use. The salt and the crystal form of the salt are an acid addition salt of a compound I and any acid in the following and a crystal form thereof: hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, benzenesulfonic acid, maleic acid, tartaric acid, oxalic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, camphorsulfonic acid, and 1, 5-naphthalene disulfonic acid. A free alkali crystal form of the compound I, the salt, and the crystal form of the salt have stable physical and chemical properties.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• C07D 403/00 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group
• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 27/02 - Ophthalmic agents
• A61P 35/00 - Antineoplastic agents
• A61P 17/16 - Emollients or protectives, e.g. against radiation
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 3/00 - Drugs for disorders of the metabolism
• A61P 37/02 - Immunomodulators
• 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 19/00 - Drugs for skeletal disorders
• A61P 15/10 - Drugs for genital or sexual disorders; Contraceptives for impotence
• A61P 7/02 - Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

A compound containing a benzene ring as shown in formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, an isotopic compound thereof, a crystal form thereof, a nitrogen oxide thereof, and a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof are provided. The compound has high P2X4 antagonistic activity, good selectivity, low toxicity and good metabolic stability. A compound containing a benzene ring as shown in formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, an isotopic compound thereof, a crystal form thereof, a nitrogen oxide thereof, and a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof are provided. The compound has high P2X4 antagonistic activity, good selectivity, low toxicity and good metabolic stability.

IPC Classes  ?

• C07D 231/56 - Benzopyrazoles; Hydrogenated benzopyrazoles
• 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 235/24 - Benzimidazoles; Hydrogenated benzimidazoles 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 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
• 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
• C07D 209/44 - Iso-indoles; Hydrogenated iso-indoles

Abstract

Disclosed is a fused ring compound and an application thereof. Disclosed is a fused ring compound represented by formula I, a pharmaceutically acceptable salt, a stereoisomer, a tautomer, an isotope compound, a crystal form, a nitrogen oxide, a solvate, or a solvate of the pharmaceutically acceptable salt thereof. The fused ring compound of the present invention has high P2X4 antagonistic activity, excellent selectivity, low toxicity and excellent metabolic stability. Disclosed is a fused ring compound and an application thereof. Disclosed is a fused ring compound represented by formula I, a pharmaceutically acceptable salt, a stereoisomer, a tautomer, an isotope compound, a crystal form, a nitrogen oxide, a solvate, or a solvate of the pharmaceutically acceptable salt thereof. The fused ring compound of the present invention has high P2X4 antagonistic activity, excellent selectivity, low toxicity and excellent metabolic stability.

IPC Classes  ?

• C07D 217/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• 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 239/72 - Quinazolines; Hydrogenated quinazolines
• C07D 237/28 - Cinnolines
• 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

Abstract

Disclosed are a compound as an inhibitor of complement factor D, and a pharmaceutical composition thereof and the use thereof. Specifically disclosed are a compound as represented by formula (I), a tautomer thereof, a stereoisomer thereof and a prodrug thereof, or a pharmaceutically acceptable salt of any one of the above-mentioned compounds, or a solvate of any one of the above-mentioned compounds. The compound has a good inhibitory activity on complement factor D, and has an excellent pharmacokinetic and pharmacodynamic activity. Formula (I)

IPC Classes  ?

• C07D 213/04 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
• C07C 229/34 - 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 containing six-membered aromatic rings
• A61K 31/4418 - Non-condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic ring directly attached to the heterocyclic ring, e.g. cyproheptadine
• A61K 31/4427 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
• A61K 31/195 - Carboxylic acids, e.g. valproic acid having an amino group
• A61P 7/00 - Drugs for disorders of the blood or the extracellular fluid
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 13/00 - Drugs for disorders of the urinary system
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 37/00 - Drugs for immunological or allergic disorders

Abstract

A compound of formula (I), and racemates, stereoisomers, tautomers, isotopic markers, solvates, polymorphs and oxynitrides of the compound, or a pharmaceutically acceptable salt thereof can be used as JNK inhibitors. A method for preparing the compound of formula (I) and a pharmaceutical composition comprising the compound of formula (I) are provided. The compound of formula (I) can be used for preparing drugs. The resulting drugs are used for treating diseases that can be treated by inhibiting JNK activity. A compound of formula (I), and racemates, stereoisomers, tautomers, isotopic markers, solvates, polymorphs and oxynitrides of the compound, or a pharmaceutically acceptable salt thereof can be used as JNK inhibitors. A method for preparing the compound of formula (I) and a pharmaceutical composition comprising the compound of formula (I) are provided. The compound of formula (I) can be used for preparing drugs. The resulting drugs are used for treating diseases that can be treated by inhibiting JNK activity.

IPC Classes  ?

• C07D 239/48 - Two nitrogen atoms
• 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 401/12 - 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 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 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

Abstract

Provided are an intermediate prepared from a ROCK inhibitor and a preparation method therefor, and a novel preparation method for a ROCK inhibitor. The intermediate has a stable nature, and high yield and purity; in addition, the preparation method is simple, reaction raw materials are common and easy to obtain, and each intermediate product may be purified by means of conventional methods, which facilitates industrial production, so as to promote the industrialization of a ROCK inhibitor. In the preparation method for a ROCK inhibitor, a new intermediate compound is used as a starting material, and the ROCK inhibitor is synthesized and obtained by passing through a substitution reaction, a hydrogenation reaction and a deprotection reaction. Compared with other routes, the raw material conversion rate in each step of this route is high. The reaction is simple and by-products are not easily produced. The preparation method may control impurities to be within a certain range, while effectively reducing or avoiding the generation of genotoxic impurities. The length of the preparation route is moderate, the production process is stable and reproducible, and the products obtained may be optimized by means of conventional beating or recrystallization to obtain a target product. The quality of the product is controllable, the safety thereof is high, and the product is suitable for industrial scale-up production.

IPC Classes  ?

• 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

Abstract

The compound represented by formula (I), and racemates, stereoisomers, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, metabolites, esters, pharmaceutically acceptable salts, or prodrugs thereof have ROCK inhibitory activity. The compound represented by formula (1) has good safety, good metabolic stability, and a low risk of potential hepatotoxicity. Further, the compound represented by formula (I) has a simple preparation method and is easy to purify, and therefore has good application prospects. The compound represented by formula (I), and racemates, stereoisomers, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, metabolites, esters, pharmaceutically acceptable salts, or prodrugs thereof have ROCK inhibitory activity. The compound represented by formula (1) has good safety, good metabolic stability, and a low risk of potential hepatotoxicity. Further, the compound represented by formula (I) has a simple preparation method and is easy to purify, and therefore has good application prospects.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• 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 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 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
• C07D 513/04 - Ortho-condensed systems
• 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 487/04 - Ortho-condensed systems

Abstract

Disclosed in the present invention are a preparation method for a heterocycloalkyl compound, and an intermediate and an application of the heterocycloalkyl compound. The present invention provides a preparation method for a compound represented by formula IN-06, comprising the following step: carrying out a ring-forming reaction and a deprotection reaction to a compound represented by formula IN-05 in an organic solvent in the presence of an acid-binding agent to obtain a compound represented by formula IN-06, the acid-binding agent being NaOH, NaH or potassium carbonate, wherein R is halogen. The preparation method of the present invention has one or more of the following advantages: having high chiral purity and facilitating industrial production.

IPC Classes  ?

• C07D 265/32 - 1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
• C07D 317/26 - Radicals substituted by doubly bound oxygen or sulfur atoms or by two such atoms singly bound to the same carbon atom

Abstract

Disclosed in the present invention are a pharmaceutical composition, a preparation, and a preparation method therefor and the use thereof. The pharmaceutical composition contains an active ingredient and a pharmaceutically acceptable excipient. The active ingredient contains a compound represented by formula A. The compound represented by formula A is selected from one, two or more of the crystal form I, the crystal form III and the crystal form V. The excipient is selected-from or comprises, but is not limited to, one, two or more of the following excipients: a diluent, a disintegrant, an adhesive, a glidant and a lubricant. The pharmaceutical composition and the preparation of the present invention have a good safety and/or stability, and a high P2X3 antagonistic activity, and have less effect on the taste.

IPC Classes  ?

• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 11/06 - Antiasthmatics
• A61P 11/08 - Bronchodilators
• A61P 11/14 - Antitussive agents
• A61P 13/00 - Drugs for disorders of the urinary system
• A61P 13/08 - Drugs for disorders of the urinary system of the prostate
• A61P 13/10 - Drugs for disorders of the urinary system of the bladder
• A61P 25/04 - Centrally acting analgesics, e.g. opioids
• A61P 25/06 - Antimigraine agents
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

An acid addition salt of a ROCK inhibitor, and a crystal form, a composition and the pharmaceutical use thereof. The acid addition salt is an acid addition salt of compound A and any one of the following acids: hydrochloric acid, p-toluenesulfonic acid, benzenesulfonic acid, maleic acid, tartaric acid, oxalic acid, fumaric acid, sulfuric acid, methanesulfonic acid, phosphoric acid, succinic acid or citric acid (A). The acid addition salt of compound A and the crystal form thereof have the characteristics of high solubility, good stability, high purity, few impurities and high bioequivalence, and are beneficial for the storage, quality control and druggability of drugs.

IPC Classes  ?

• 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

Abstract

Disclosed in the present invention are a crystal form of a compound, a composition containing the crystal form, a preparation method therefor and the use thereof. The crystal forms, i.e. crystal form I and crystal form II, of a compound of formula A have stable chemical properties. Specifically, compared with an amorphous substance, the content of impurities generated after the crystal forms are placed is reduced; and compared with an amorphous substance, the crystal forms of the present invention are all relatively stable under high temperature or high humidity conditions, which is more conducive to the quality control and druggability of a drug.

IPC Classes  ?

• 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 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
• 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 31/415 - 1,2-Diazoles
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

An acid addition salt of a ROCK inhibitor, and a crystal form, a composition and the pharmaceutical use thereof. The acid addition salt is an acid addition salt of compound A and any one of the following acids: hydrochloric acid, p-toluenesulfonic acid, benzenesulfonic acid, maleic acid, tartaric acid, oxalic acid, fumaric acid, sulfuric acid, methanesulfonic acid, phosphoric acid, succinic acid or citric acid (A). The acid addition salt of compound A and the crystal form thereof have the characteristics of high solubility, good stability, high purity, few impurities and high bioequivalence, and are beneficial for the storage, quality control and druggability of drugs.

IPC Classes  ?

• 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 31/40 - 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 31/415 - 1,2-Diazoles
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/00 - Drugs for disorders of the nervous system

Abstract

Disclosed are a heterocyclic compound, and an intermediate thereof, a preparation method therefor and the use thereof. Namely, provided are a heterocyclic compound as shown in formula I-a, and a tautomer and a pharmaceutically acceptable salt thereof, wherein the compound has a good water solubility and pharmacokinetic properties.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys

Abstract

Disclosed are an aromatic compound represented by formula I, and a pharmaceutically acceptable salt, stereoisomer, tautomer, or isotopic compound thereof. The compound has high P2X4 antagonistic activity, good safety, and good pharmacokinetic properties.

IPC Classes  ?

• C07C 311/46 - Y being a hydrogen or a carbon atom
• A61K 31/145 - Amines, e.g. amantadine having sulfur atoms, e.g. thiurams (N—C(S)—S—C(S)—N or N—C(S)—S—S—C(S)—N); Sulfinylamines (—N=SO); Sulfonylamines (—N=SO2)
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 13/00 - Drugs for disorders of the urinary system
• A61P 15/00 - Drugs for genital or sexual disorders; Contraceptives
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 25/06 - Antimigraine agents
• A61P 35/00 - Antineoplastic agents
• A61P 27/00 - Drugs for disorders of the senses

Abstract

Certain compounds are lysophosphatidic acid receptor antagonists have high LPAR1 antagonist activity and selectivity, low toxicity, good metabolic stability, promising pharmaceutical development prospects, and may be used for preventing or treating LPAR1-related diseases or illnesses. The IC50 values of some of the compounds may be as low as 300 nM or below, even 50 nM or below. In addition, CC50 value range of the compounds may be as high as 200 μM or above. Furthermore, the compounds have good metabolic stability in humans, mice and rats.

IPC Classes  ?

• 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
• C07D 263/32 - Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
• A61K 31/421 - 1,3-Oxazoles, e.g. pemoline, trimethadione
• A61K 31/415 - 1,2-Diazoles
• 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
• A61K 31/42 - Oxazoles
• C07D 261/14 - Nitrogen atoms
• C07D 261/08 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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 277/24 - Radicals substituted by oxygen atoms
• A61K 31/426 - 1,3-Thiazoles
• A61K 31/4164 - 1,3-Diazoles
• 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 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 275/02 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
• A61K 31/425 - Thiazoles
• A61P 11/00 - Drugs for disorders of the respiratory system

Abstract

Certain triazole compounds have good LPAR1 antagonistic activity and selectivity, low toxicity, and good metabolic stability, and can be used for preventing or treating the LPAR1-related disease or disorder. The IC50 value of some triazole compounds can be below 300 nM, even 50 nM. The range of CC50 of the triazole compounds can be greater than 200 μM. They also show good metabolic stability in human, fancy rats, and house mice.

IPC Classes  ?

• C07D 249/06 - 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
• C07D 263/22 - Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
• 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 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 413/14 - 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 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 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 213/65 - One oxygen atom attached in position 3 or 5

Abstract

Provided are a compound shown in formula (I) below, and racemates, stereoisomers, tautomers, isotopic markers, solvates, polymorphs and oxynitrides of the compound, or a pharmaceutically acceptable salt thereof, wherein same can be used as JNK inhibitors. Also provided are a method for preparing the compound shown in formula (I), a pharmaceutical composition comprising the compound shown in formula (I), and the use of the compound shown in formula (I) for preparing drugs, wherein the drugs are used for treating diseases which can be treated by inhibiting JNK activity.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• A61P 35/00 - Antineoplastic agents

Abstract

A ROCK inhibitor represented by formula (I), and a preparation method therefor and a use thereof. The ROCK inhibitor has excellent ROCK inhibition activity, particularly shows good selective inhibition on ROCK2 kinase, has good safety and metabolic stability, and is high in bioavailability. The preparation method for the ROCK inhibitor is simple, and the ROCK inhibitor is easy to purify, and therefore has a good application prospect.

IPC Classes  ?

• C07D 471/06 - Peri-condensed systems
• A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis
• C07D 293/10 - Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms condensed with carbocyclic rings or ring systems
• 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 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

Abstract

A ROCK inhibitor represented by formula (I), and a preparation method therefor and a use thereof. The ROCK inhibitor has excellent ROCK inhibition activity, particularly shows good selective inhibition on ROCK2 kinase, has good safety and metabolic stability, and is high in bioavailability. The preparation method for the ROCK inhibitor is simple, and the ROCK inhibitor is easy to purify, and therefore has a good application prospect.

IPC Classes  ?

• C07D 471/06 - Peri-condensed systems
• 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 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 293/10 - Heterocyclic compounds containing rings having nitrogen and selenium or nitrogen and tellurium, with or without oxygen or sulfur atoms, as the ring hetero atoms condensed with carbocyclic rings or ring systems
• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 35/00 - Antineoplastic agents
• A61P 3/08 - Drugs for disorders of the metabolism for glucose homeostasis

Abstract

Provided are a crystalline form of a compound represented by formula A, the crystalline form being crystalline form I, crystalline form II, crystalline form III, crystalline form IV, crystalline form V, crystalline form VI, crystalline form VII, crystalline form VIII or crystalline form IX, a preparation method therefor, a composition thereof, and an application thereof in the preparation of a P2X3 receptor antagonist or an application thereof in the preparation of drugs preventing and/or treating pains, urinary tract illness or respiratory system illness. The compound has high P2X3 antagonist activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• 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
• A61P 11/14 - Antitussive agents
• A61P 25/04 - Centrally acting analgesics, e.g. opioids

Abstract

Provided are a crystalline form of a compound represented by formula A, the crystalline form being crystalline form I, crystalline form II, crystalline form III, crystalline form IV, crystalline form V, crystalline form VI, crystalline form VII, crystalline form VIII or crystalline form IX, a preparation method therefor, a composition thereof, and an application thereof in the preparation of a P2X3 receptor antagonist or an application thereof in the preparation of drugs preventing and/or treating pains, urinary tract illness or respiratory system illness. The compound has high P2X3 antagonist activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• 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
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• A61P 11/14 - Antitussive agents
• A61P 13/00 - Drugs for disorders of the urinary system
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 25/04 - Centrally acting analgesics, e.g. opioids

Abstract

Disclosed is a heterocyclic compound as represented by formula (I), a tautomer thereof, or a pharmaceutically acceptable salt thereof. The compound has better inhibitory activity on TRPC5, has good metabolic stability in liver micro-particles, and has good clinical pharmacokinetic properties.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys

Abstract

Disclosed is a heterocyclic compound as represented by formula (I), a tautomer thereof, or a pharmaceutically acceptable salt thereof. The compound has better inhibitory activity on TRPC5, has good metabolic stability in liver micro-particles, and has good clinical pharmacokinetic properties.

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys

Abstract

Disclosed is a fused ring compound and an application thereof. Disclosed is a fused ring compound represented by formula I, a pharmaceutically acceptable salt, a stereoisomer, a tautomer, an isotope compound, a crystal form, a nitrogen oxide, a solvate, or a solvate of the pharmaceutically acceptable salt thereof. The fused ring compound of the present invention has high P2X4 antagonistic activity, excellent selectivity, low toxicity, and excellent metabolic stability.

IPC Classes  ?

• C07D 217/24 - Oxygen atoms
• C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
• 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 215/38 - Nitrogen atoms
• C07D 217/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• 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 217/12 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
• 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 239/84 - Nitrogen atoms
• C07D 239/72 - Quinazolines; Hydrogenated quinazolines
• C07D 237/28 - Cinnolines
• C07C 311/15 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
• C07D 401/02 - 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
• C07D 217/06 - 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 with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
• C07D 217/04 - 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 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• 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
• A61K 31/472 - Non-condensed isoquinolines, e.g. papaverine
• A61K 31/47 - Quinolines; Isoquinolines
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
• A61P 11/14 - Antitussive agents

Abstract

Disclosed is a fused ring compound and an application thereof. Disclosed is a fused ring compound represented by formula I, a pharmaceutically acceptable salt, a stereoisomer, a tautomer, an isotope compound, a crystal form, a nitrogen oxide, a solvate, or a solvate of the pharmaceutically acceptable salt thereof. The fused ring compound of the present invention has high P2X4 antagonistic activity, excellent selectivity, low toxicity, and excellent metabolic stability.

IPC Classes  ?

• C07D 217/24 - Oxygen atoms
• A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
• A61P 11/14 - Antitussive agents
• C07C 311/15 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
• C07D 215/38 - Nitrogen atoms
• 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 217/04 - 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 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• C07D 217/06 - 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 with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates
• C07D 217/12 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
• C07D 217/22 - Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
• C07D 217/26 - Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• C07D 237/28 - Cinnolines
• C07D 239/72 - Quinazolines; Hydrogenated quinazolines
• C07D 239/84 - Nitrogen atoms
• C07D 401/02 - 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
• 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 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

Abstract

Provided are a compound containing a benzene ring as shown in formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, an isotopic compound thereof, a crystal form thereof, a nitrogen oxide thereof, and a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof. The compound has high P2X4 antagonistic activity, good selectivity, low toxicity, and good metabolic stability.

IPC Classes  ?

• C07D 231/56 - Benzopyrazoles; Hydrogenated benzopyrazoles
• C07D 209/04 - Indoles; Hydrogenated indoles
• C07D 209/44 - Iso-indoles; Hydrogenated iso-indoles
• C07D 235/04 - Benzimidazoles; Hydrogenated benzimidazoles
• C07D 487/04 - Ortho-condensed systems

Abstract

Provided are a compound containing a benzene ring as shown in formula I, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof, an isotopic compound thereof, a crystal form thereof, a nitrogen oxide thereof, and a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof. The compound has high P2X4 antagonistic activity, good selectivity, low toxicity, and good metabolic stability.

IPC Classes  ?

• C07D 231/56 - Benzopyrazoles; Hydrogenated benzopyrazoles
• C07D 235/04 - Benzimidazoles; Hydrogenated benzimidazoles
• C07D 209/04 - Indoles; Hydrogenated indoles
• C07D 209/44 - Iso-indoles; Hydrogenated iso-indoles
• C07D 487/04 - Ortho-condensed systems
• A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system

Abstract

The compound represented by formula (I), and racemates, stereoisomers, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, metabolites, esters, pharmaceutically acceptable salts, or prodrugs thereof. The compound represented by formula (I) has excellent ROCK inhibitory activity. In addition, the compound represented by formula (I) has good safety and metabolic stability. Furthermore, the compound represented by formula (I) has a low risk of potential hepatotoxicity. Finally, the compound represented by formula (I) has a simple preparation method and is easy to purify, and therefore has good application prospects.

IPC Classes  ?

• 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 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 471/04 - Ortho-condensed systems

Abstract

The compound represented by formula (I), and racemates, stereoisomers, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, metabolites, esters, pharmaceutically acceptable salts, or prodrugs thereof. The compound represented by formula (I) has excellent ROCK inhibitory activity. In addition, the compound represented by formula (I) has good safety and metabolic stability. Furthermore, the compound represented by formula (I) has a low risk of potential hepatotoxicity. Finally, the compound represented by formula (I) has a simple preparation method and is easy to purify, and therefore has good application prospects.

IPC Classes  ?

• 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 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 471/04 - Ortho-condensed systems
• 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 31/415 - 1,2-Diazoles
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 43/00 - Drugs for specific purposes, not provided for in groups

Abstract

Provided are a compound as shown in formula (I), which formula is as follows, and racemates, stereoisomers, tautomers, isotopic markers, solvates, polymorphs and oxynitrides of the compound, or a pharmaceutically acceptable salt thereof, wherein same can be used as JNK inhibitors. Also provided are a method for preparing the compound shown in formula (I), a pharmaceutical composition comprising the compound shown in formula (I), and the use of the compound shown in formula (I) for preparing drugs, wherein the drugs are used for treating diseases which can be treated by inhibiting JNK activity.

IPC Classes  ?

• C07D 239/48 - Two nitrogen atoms
• C07D 239/47 - One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
• C07D 239/38 - One sulfur atom
• A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• 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 35/00 - Antineoplastic agents
• A61P 3/00 - Drugs for disorders of the metabolism
• 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 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 401/12 - 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 405/02 - 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
• 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

Abstract

A pharmaceutical preparation includes a first active component, a second active component and pharmaceutically acceptable excipients. The first active component is at least one selected from the group consisting of a neutral endopeptidase inhibitor and a precursor, an active metabolite, a stereoisomer, a pharmaceutically acceptable salt, a prodrug and a solvate thereof. The second active component is at least one selected from the group consisting of a compound represented by the following formula (I) or a precursor, an active metabolite, a stereoisomer, a pharmaceutically acceptable salt, a prodrug and a solvate thereof. The pharmaceutically acceptable excipients include one or more disintegrants and/or one or more fillers.

IPC Classes  ?

• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61K 47/38 - Cellulose; Derivatives thereof
• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
• A61K 47/12 - Carboxylic acids; Salts or anhydrides thereof
• A61K 47/02 - Inorganic compounds
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Abstract

The compound shown in formula I, and racemates, stereoisomers, tautomers, isotopic markers, nitrogen oxides, solvates, polymorphs, metabolites, esters, pharmaceutically acceptable salts, or prodrugs thereof. The compound shown in formula I has excellent ROCK inhibitory activity. In addition, the compound shown in formula I has good safety and metabolic stability. Furthermore, the compound shown in formula I has a low risk of cardiotoxicity. Finally, the compound shown in formula I has a simple preparation method and is easy to purify, and therefore has good application prospects. (I)

IPC Classes  ?

• C07D 487/04 - Ortho-condensed systems
• A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
• A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 25/00 - Drugs for disorders of the nervous system
• A61P 11/00 - Drugs for disorders of the respiratory system
• A61P 27/02 - Ophthalmic agents
• A61P 35/00 - Antineoplastic agents
• A61P 7/02 - Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• A61P 37/02 - Immunomodulators
• 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 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
• A61P 15/10 - Drugs for genital or sexual disorders; Contraceptives for impotence
• A61P 27/06 - Antiglaucoma agents or miotics
• A61P 11/06 - Antiasthmatics
• A61P 19/10 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
• 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 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

505050 thereof can be greater than 200 µM. The compounds in the present invention have good metabolic stability in human, fancy rats, and house mice. The preparation method for the compounds in the present invention is simple, requires mild operation conditions, has high product yield, and is suitable for industrial production.

IPC Classes  ?

• C07D 249/06 - 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
• 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
• A61K 31/4192 - 1,2,3-Triazoles
• 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 11/06 - Antiasthmatics
• A61P 35/00 - Antineoplastic agents

Abstract

505050 value range may be as high as 200μM or above. Furthermore, the compounds have good metabolic stability in humans, mice and rats, and such excellent inhibitory activity is very promising for their application as LPAR1 inhibitors in the described diseases and illnesses. The preparation method for the compounds is simple, has mild reaction conditions and high product yield, and is suitable for industrial production.

IPC Classes  ?

• C07D 263/32 - Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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 275/02 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
• C07D 277/02 - Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
• C07D 231/40 - Acylated on said nitrogen atom
• 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 31/335 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
• A61K 31/38 - Heterocyclic compounds having sulfur as a ring hetero atom
• A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• A61P 11/06 - Antiasthmatics
• A61P 35/00 - Antineoplastic agents

Abstract

Disclosed by the present invention is a heterocyclic compound, an intermediate, a preparation method therefor and an application thereof. Provided by the present invention are a heterocyclic compound as shown in formula I, and a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, a solvate, a metabolite, an ester, a pharmaceutically acceptable salt or a prodrug thereof. The heterocyclic compound has a high P2X3 antagonistic activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• 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 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
• 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 11/14 - Antitussive agents
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

Disclosed by the present invention is a heterocyclic compound, an intermediate, a preparation method therefor and an application thereof. Provided by the present invention are a heterocyclic compound as shown in formula I, and a stereoisomer, a geometric isomer, a tautomer, a nitrogen oxide, a hydrate, a solvate, a metabolite, an ester, a pharmaceutically acceptable salt or a prodrug thereof. The heterocyclic compound has a high P2X3 antagonistic activity, and has good selectivity, low toxicity, good metabolic stability and little taste influence.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• 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 31/4545 - 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 11/14 - Antitussive agents
• A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The present disclosure belongs to the field of chemical synthesis, and in particular relates to an ammonium carboxylate compound, a crystalline form and an amorphous form, and a preparation method thereof. The present disclosure prepares the compound and the crystalline form I and its single crystal, amorphous form and crystalline form II thereof. The compound, the crystalline forms, the single crystal and the amorphous form can stably exist and exhibit good solid forms, suitable for medicine-making. Furthermore, these products possess high purity and less single impurity. Moreover, the preparation methods of the present disclosure are easy to implement due to the simple processes with mild reaction conditions, and could produce products of high yield and high purity without complex purification steps. Furthermore, the preparation methods may facilitate safety, environmental protection, and industrial production.

IPC Classes  ?

• C07D 295/027 - 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 containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
• C07C 229/34 - 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 containing six-membered aromatic rings
• C07C 227/20 - 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 by hydrolysis of N-acylated amino acids or derivatives thereof, e.g. hydrolysis of carbamates
• C07C 231/02 - Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• C07C 231/12 - Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups

Abstract

The present invention relates to a pharmaceutical composition comprising: (a) at least one neutral endopeptidase inhibitor or a pharmaceutically acceptable salt or ester thereof, (b) at least one compound represented by formula (I) or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier. Combined administration showed better medicinal effects than separate administration.

IPC Classes  ?

• A61K 31/4245 - Oxadiazoles
• A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
• 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 9/12 - Antihypertensives
• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene

Abstract

The preparation method for the compound, composition and application thereof in preparing an angiotensin II receptor antagonist or application in preparing medicine for preventing and/or treating hypertension, chronic heart failure and diabetic nephropathy. After entering a human body, when releasing azilsartan, the compound releases hydroxyligustrazine or NO at the same time, thus generating a synergistic effect with azilsartan. The compound therefore has stronger and longer blood pressure lowering effect, more obvious and longer lasting heart rate lowering effect and high safety, and achieves ideal protective effect for heart and kidney functions.

IPC Classes  ?

• 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
• 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
• A61P 9/12 - Antihypertensives

Abstract

The present disclosure provides a triazole antibacterial derivative and a pharmaceutical composition thereof and a use thereof and in particular relates to a compound represented by the following formula (I), and a racemate, a stereoisomer, a tautomer, an oxynitride or a pharmaceutically acceptable salt thereof: The compound of the present disclosure has a desirable water solubility and can be formulated into an injection for use without adding a cosolvent having a potential safety risk (such as hydroxypropyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin, and the like), facilitating drug administration for patients, and greatly improving clinical safety. The drug can be used even by patients with moderate or severe renal impairment, thereby expanding the application scope of the drug.

IPC Classes  ?

• 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 403/06 - 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
• C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
• C07H 13/04 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
• A61P 31/10 - Antimycotics

Abstract

A complex disintegrant composition for oral solid preparation, comprising a disintegrant and a disintegrating aid, the disintegrant being a hygroscopic expansion type disintegrant, the disintegrating aid being a soluble small molecule substance or a gas-producing type salt. An oral solid preparation, comprising an active ingredient, said complex disintegrant composition, an excipient and a lubricant.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61P 9/12 - Antihypertensives
• A61K 31/4245 - Oxadiazoles
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings

Abstract

The invention discloses an oral solid preparation containing any one, or a mixture of two or more of crystalline form I, II, III, and IV of the compound represented by formula (A). The oral solid preparation of the present invention disintegrates rapidly, increasing dissolution rate thereof, thereby improving bioavailability. In particular, it is possible to solve the problem that an active material (active ingredient), which is high hygroscopic and becomes sticky after moisture absorption, can not be effectively disintegrated by conventional disintegrants. The present invention further relates to a use of the oral solid preparation in preparing an angiotensin II receptor antagonist or a use thereof in preparing medicine for preventing and/or treating hypertension, chronic heart failure and diabetic nephropathy.

IPC Classes  ?

• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 9/12 - Antihypertensives
• A61K 9/00 - Medicinal preparations characterised by special physical form
• A61K 9/20 - Pills, lozenges or tablets

Abstract

The present invention provides a medicine composition preparation method, comprising: (1) taking a first active component, a second active component, a first ingredient and a second ingredient; (2) mixing the first active component, the second active component and the first ingredient to disperse the first active component and the second active component in the first ingredient added therein to obtain a first mixture; (3) preparing the first mixture by adopting dry granulation to obtain a first particle; and (4) adding the second ingredient into the first particle by means of additional method, and mixing to obtain a second mixture.

IPC Classes  ?

• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/4245 - Oxadiazoles
• A61K 31/4164 - 1,3-Diazoles
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• 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
• A61P 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Disclosed in the present invention are a pharmaceutical formulation and use thereof. The formulation comprises a first active component, a second active component and a pharmaceutically acceptable adjuvant. The first active component is at least one selected from neutral endopeptidase inhibitors and precursors, active metabolites, stereoisomers, pharmaceutically acceptable salts, prodrugs and solvates thereof. The second active component is at least one selected from compounds represented by formula (I) or precursors, active metabolites, stereoisomers, pharmaceutically acceptable salts, prodrugs and a solvates thereof. The pharmaceutically acceptable adjuvant comprises one or more disintegrants and/or one or more fillers. The formulation can ameliorate the problem that conventional adjuvants cannot dissolve out active ingredients effectively.

IPC Classes  ?

• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/4245 - Oxadiazoles
• A61K 31/4164 - 1,3-Diazoles
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• 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
• A61P 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

Provided are a preparation method for a crystalline form of the compound represented by formula (A), as well as a method for preparation thereof, a composition thereof, and an application thereof in preparing an angiotensin II receptor antagonist or an application in preparing a drug for preventing and/or treating hypertension, chronic heart failure and diabetic nephropathy.

IPC Classes  ?

• 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
• A61P 9/12 - Antihypertensives
• A61P 9/06 - Antiarrhythmics
• A61K 31/4245 - Oxadiazoles
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

The present invention provides a method for preparing a benzimidazole derivative with low impurity content. The method of present invention comprises dissolving an initial product of a compound of formula I below with an organic solvent S1, stirring and crystallizing the solution, and drying the crystal to obtain a purified compound of formula I, wherein the organic solvent S1 may be selected from one, two or more of an ester solvent, an alkane solvent, an ether solvent, a nitrile solvent, an alcohol solvent, a halogenated hydrocarbon solvent, and a ketone solvent. The preparation method of the present invention noticeably simplifies processing, and obtains a high-purity product in high yield, capable of significantly reducing the amount of impurities in the product.

IPC Classes  ?

• 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 413/08 - 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 alicyclic rings
• A61K 31/4245 - Oxadiazoles
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys

Abstract

Disclosed is the use of a saccharide compound in the preparation of a drug. The present invention relates to the treatment and/or prevention of lipid metabolic disorders or diseases or conditions related thereto, including hyperlipidemia, arteriosclerosis or the increased risk of other related cardiovascular events.

IPC Classes  ?

• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
• A61K 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
• A61K 31/726 - Glycosaminoglycans, i.e. mucopolysaccharides
• 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 9/00 - Drugs for disorders of the cardiovascular system
• A61P 3/06 - Antihyperlipidemics
• A61P 3/00 - Drugs for disorders of the metabolism

Abstract

Disclosed is a pharmaceutical composition, comprising a first component and a second component, wherein the first component is selected from at least one of an ASK1 inhibitor and a precursor, an active metabolite, a stereisomer, a pharmaceutically acceptable salt, an ester and a solvate thereof; and the second component is selected from at least one of a PPAR modifier, and a precursor, an active metabolite, a stereisomer, a pharmaceutically acceptable salt, an ester and a solvate thereof. Also disclosed is a pharmaceutical preparation comprising the pharmaceutical composition. Also disclosed is a use of the pharmaceutical composition in the preparation of a medicament for treating and/or preventing nonalcoholic fatty liver or nonalcoholic steatohepatitis, reducing levels of total cholesterol, lowering liver coefficient, increasing high-density lipoprotein cholesterol, and/or improving NAS score and/or fibrosis score.

IPC Classes  ?

• A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 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 3/06 - Antihyperlipidemics

Abstract

The present disclosure provides a posaconazole derivative, a pharmaceutical composition and use thereof, which specifically include a compound represented by the following formula (I), a racemate, stereoisomer, tautomer, oxynitride, or a pharmaceutically acceptable salt thereof: The compounds of the present disclosure have strong antifungal activity, high safety, and good water solubility, without the need for the addition of a cosolvent (such as hydroxypropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, and the like) with potential safety risks. Furthermore, the formulation process of the compound could have less difficulty and less cost, and therefore can be used to prepare improved antifungal drugs.

IPC Classes  ?

• A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
• 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 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• A61P 31/10 - Antimycotics
• C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
• A61K 31/133 - Amines, e.g. amantadine having hydroxy groups, e.g. sphingosine
• C07H 5/04 - Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to nitrogen

Abstract

The present invention falls within the field of preparation methods for pharmaceutical compounds, and in particular relates to preparation and analysis methods of a benzimidazole derivative. The methods comprise recrystallizing and pulping the mixture comprising a compound of formula I using a solvent, and filtering and drying same to obtain the product. The preparation process of the present invention is simple in operation, and compared to the prior art, has a shorter operation cycle, a lower cost, a higher yield, and a lower emission load in terms of the three wastes, a higher purity of the compound obtained, and a lower content of the rearrangement product. The purification process of the present invention improves the technical problem that existing column chromatography cannot enlarge the purification scale, and same also meets the requirements of industrialized production.

IPC Classes  ?

• 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
• 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 493/04 - Ortho-condensed systems
• C07D 498/18 - Bridged systems

Abstract

The present invention relates to the field of chemical synthesis, and in particular to an ammonium carboxylate compound, a crystal form and an amorphous substance thereof, and a preparation method therefor. The present invention prepares a compound and a crystal form I, a single crystal, an amorphous substance and a crystal form II thereof. The compound, the crystal forms, the single crystal and the amorphous substance can stably exist, present good solid form, are suitable for patent medicine, and are high in product purity and less individual impurity. The preparation method of the present invention is simple in process, mild in reaction conditions, and high in product yield, and is easy to implement. The product does not require several purification, is high in purity and safety and environmental protection, and is suitable for industrial production.

IPC Classes  ?

• C07C 233/47 - Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• C07C 211/05 - Mono-, di- or tri-ethylamine
• C07C 215/08 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with only one hydroxy group and one amino group bound to the carbon skeleton
• C07D 295/027 - 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 containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• 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 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

The present invention provides a triazole antibacterial derivative and a pharmaceutical composition and a use thereof, and in particular relates to a compound represented by the following formula (I), and a racemate, a stereoisomer, a tautomer, and a nitrogen oxide thereof or their pharmaceutically acceptable salts, as shown in formula (I). The compound of the present invention has a desirable water solubility and can be formulated into an injection for use without adding a cosolvent having a potential safety risk (such as hydroxypropyl-β-cyclodextrin and sulfobutylether-β-cyclodextrin), facilitating drug administration for patients, and greatly improving clinical safety. The drug can be used even by patients with moderate or severe renal impairment, thereby expanding the application scope of the drug.

IPC Classes  ?

• 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 403/06 - 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
• C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
• C07H 13/04 - Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
• C07H 1/00 - Processes for the preparation of sugar derivatives
• A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
• A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• A61K 31/7064 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
• A61P 31/10 - Antimycotics

Abstract

The present invention relates to a pharmaceutical composition comprising: (a) at least one neutral endopeptidase inhibitor or a pharmaceutically acceptable salt or ester thereof, (b) at least one compound represented by formula (I) or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier. Combined administration showed better medicinal effects than separate administration.

IPC Classes  ?

• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/4245 - Oxadiazoles
• A61K 31/4164 - 1,3-Diazoles
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61K 31/216 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
• A61K 31/192 - Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
• 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
• A61P 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Abstract

The invention discloses an oral solid preparation containing any one, or a mixture of two or more of crystalline form I, II, III, and IV of the compound represented by formula (A). The oral solid preparation of the present invention disintegrates rapidly, increasing dissolution rate thereof, thereby improving bioavailability. In particular, it is possible to solve the problem that an active material (active ingredient), which is high hygroscopic and becomes sticky after moisture absorption, can not be effectively disintegrated by conventional disintegrants. The present invention further relates to a use of the oral solid preparation in preparing an angiotensin II receptor antagonist or a use thereof in preparing medicine for preventing and/or treating hypertension, chronic heart failure and diabetic nephropathy.

IPC Classes  ?

• 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
• 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 493/04 - Ortho-condensed systems
• C07D 498/18 - Bridged systems
• A61K 31/42 - Oxazoles
• A61K 31/45 - Non-condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61P 9/12 - Antihypertensives
• A61P 9/06 - Antiarrhythmics
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

A complex disintegrant composition for oral solid preparation, comprising a disintegrant and a disintegrating aid, the disintegrant being a hygroscopic expansion type disintegrant, the disintegrating aid being a soluble small molecule substance or a gas-producing type salt. An oral solid preparation, comprising an active ingredient, said complex disintegrant composition, an excipient and a lubricant.

IPC Classes  ?

• A61K 9/20 - Pills, lozenges or tablets
• A61K 47/38 - Cellulose; Derivatives thereof
• A61K 47/36 - Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• A61K 47/32 - Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers
• A61K 47/02 - Inorganic compounds
• A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• A61K 31/4245 - Oxadiazoles
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Abstract

Provided are a preparation method for a crystalline form of the compound represented by formula (A), as well as a method for preparation thereof, a composition thereof, and an application thereof in preparing an angiotensin II receptor antagonist or an application in preparing a drug for preventing and/or treating hypertension, chronic heart failure and diabetic nephropathy.

IPC Classes  ?

• 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
• A61K 31/4245 - Oxadiazoles
• A61P 9/12 - Antihypertensives
• A61P 9/06 - Antiarrhythmics
• A61P 9/00 - Drugs for disorders of the cardiovascular system

Abstract

The preparation method for the compound, composition and application thereof in preparing an angiotensin II receptor antagonist or application in preparing medicine for preventing and/or treating hypertension, chronic heart failure and diabetic nephropathy. After entering a human body, when releasing azilsartan, the compound releases hydroxyligustrazine or NO at the same time, thus generating a synergistic effect with azilsartan. The compound therefore has stronger and longer blood pressure lowering effect, more obvious and longer lasting heart rate lowering effect and high safety, and achieves ideal protective effect for heart and kidney functions.

IPC Classes  ?

• C07D 413/08 - 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 alicyclic 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
• A61K 31/4245 - Oxadiazoles
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61P 9/12 - Antihypertensives
• A61P 9/04 - Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• A61P 13/12 - Drugs for disorders of the urinary system of the kidneys

Abstract

The present invention provides a posaconazole derivative and a pharmaceutical composition and use thereof. Specifically, the present invention includes a compound represented by formula (I) below, a racemate, stereoisomer, tautomer, and oxynitride thereof, or a pharmaceutically acceptable salt thereof. The compound of the present invention has strong antifungal activity, high safety, and good water solubility, and does not need to add a cosolvent with a potential safety risk (such as hydroxypropyl-β-cyclodextrin or sulfobutylether-β-cyclodextrin). Moreover, preparing the compound into a formulation involves less difficulty and cost. The compound can be used for preparing an improved antifungal drug.

IPC Classes  ?

• C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
• 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 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
• A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• A61P 31/10 - Antimycotics

Abstract

The invention belongs to the technical field of pharmaceutical chemistry, and particularly pertains to benzimidazole derivatives, and preparation process and pharmaceutical uses thereof. Benzimidazole derivatives include Ligustrazine and NO donor derivatives. The kind of the compounds can rapidly release Ligustrazine or No in vivo, so that they can produce effective synergetic effects with Azilsartan, to enhance the anti-hypertension effect, and reduce adverse effects, and the released Ligustrazine can produce ideal protection to patients' livers and kidneys, thereby filling blanks in the prior art.

IPC Classes  ?

• 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
• A61K 31/4245 - Oxadiazoles
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic 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
• C07D 493/04 - Ortho-condensed systems
• C07D 498/18 - Bridged systems
• 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

Abstract

The present invention belongs to the technical field of the pharmaceutical chemistry. Disclosed specifically are benzimidazole derivatives, a preparation method therefor and a medicinal use thereof. The benzimidazole derivatives comprise ligustrazine and NO donor derivatives. In vivo, ligustrazine or NO can be released from the derivatives quickly, so that effective synergistic effect with Azilsartan is achieved, anti-hypertension curative effect is improved, adverse reactions are reduced, rather ideal protective effects on livers and kidneys of patients are achieved, and the blank of the prior art is filled.

IPC Classes  ?

• 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
• 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 493/04 - Ortho-condensed systems
• C07D 498/18 - Bridged systems
• A61K 31/4245 - Oxadiazoles
• A61K 31/497 - Non-condensed pyrazines containing further heterocyclic rings
• A61K 31/501 - Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
• A61P 9/12 - Antihypertensives
• A61P 9/06 - Antiarrhythmics
• A61P 9/00 - Drugs for disorders of the cardiovascular system
• A61P 5/50 - Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin

Abstract

Methods and compositions comprising ornithine and/or aspartate that are useful for lowering serum glucose level, treating diabetes or hyperglycemia are described. Methods of using compositions comprising ornithine and/or aspartate for ameliorating the side-effect induced by a therapeutic agent (e.g., anti-hyperglycemic agents) are also described.

IPC Classes  ?

• A61K 31/198 - Alpha-amino acids, e.g. alanine, edetic acid (EDTA)
• A61K 31/155 - Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (HN=C(OH)NH2), isothiourea (HN=C(SH)—NH2)
• A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics