The present invention relates to the technical field of medicines, and provides a fused ring compound, a pharmaceutical composition containing the same, and use of the fused ring compound. The compound has a structure as shown in formula (I), or a tautomer, a mesomer, a racemat, an enantiomer, a diastereoisomer or a mixture thereof, a metabolite, a metabolic precursor, an isotope substitution form, a pharmaceutically acceptable salt, a hydrate, a solvate, a polymorph or a cocrystal thereof. The compound provided by the present invention can be used for treating cancers caused by KRAS mutation. The cancers caused by KRAS mutation are selected from one or more cancers caused by KRAS G12C, KRAS G12V, KRAS G12A and G12D mutations. In particular, the compound can serve as a G12D inhibitor and has relatively high inhibitory activity.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 471/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups
The present invention relates to a compound as represented by general formula Ⅰ, or a pharmaceutically acceptable salt, stereoisomer, ester, prodrug or solvate thereof. Experimental results indicate that the compound has high inhibitory activity and PAKI/II selectivity for PAK4 kinase, has good liver microsomal stability and rat pharmacokinetics (PK) properties, and in particular, has a low risk of hERG cardiotoxicity. Compared with compounds disclosed in the prior art, the compound represents a notable progress.
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 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
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
The present invention provides a pharmaceutical composition, comprising a GLP-I receptor agonist or an analog thereof, and further comprising one or more of the following components: a pro-penetrating agent, a basic substance, and an adhesive material. The technology can not only greatly improve the bioavailability and solve the problem of a low response rate for patients, but also is expected to solve the problem of low administration compliance of previous marketed medicines; and the prescription process is simple and stable, and production and transportation are convenient.
A compound as a BTK inhibitor or an HER2 inhibitor, a preparation method therefor, and a use thereof. The compound comprises a structure as shown in formula II or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, or a mixture form thereof, and a pharmaceutically acceptable hydrate, a solvate, or salt. The BTK protein kinase inhibitor of the present invention has strong inhibitory activity on wild-type BTK or mutated BTK (C481S), and some of the compounds have high brain permeability; the HER2 inhibitor of the present invention has good HER2 kinase inhibitory activity and high blood-brain barrier transmittance; and the compound of the present invention has good pharmacokinetic properties and a good application prospect.
A compound as a BTK inhibitor or an HER2 inhibitor, a preparation method therefor, and a use thereof. The compound comprises a structure as shown in formula II or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, or a mixture form thereof, and a pharmaceutically acceptable hydrate, a solvate, or salt. The BTK protein kinase inhibitor of the present invention has strong inhibitory activity on wild-type BTK or mutated BTK (C481S), and some of the compounds have high brain permeability; the HER2 inhibitor of the present invention has good HER2 kinase inhibitory activity and high blood-brain barrier transmittance; and the compound of the present invention has good pharmacokinetic properties and a good application prospect.
The present invention relates to the technical field of medicines, and provides a fused ring compound, a pharmaceutical composition containing the same, and use of the fused ring compound. The compound has a structure as shown in formula (I), or a tautomer, a mesomer, a racemat, an enantiomer, a diastereoisomer or a mixture thereof, a metabolite, a metabolic precursor, an isotope substitution form, a pharmaceutically acceptable salt, a hydrate, a solvate, a polymorph or a eutectic substance thereof. The compound provided by the present invention can be used for treating cancers caused by KRAS mutation. The cancers caused by KRAS mutation are selected from one or more cancers caused by KRAS G12C, KRAS G12V, KRAS G12A and G12D mutations. In particular, the compound can serve as a G12D inhibitor and has relatively high inhibitory activity.
C07D 471/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
The present invention discloses a compound as a sodium channel regulator, and this type of compound can effectively inhibit and block the activity of Nav1.8 ion channel, a subtype of voltage-gated sodium channels, and can be used as a specific Nav1.8 inhibitor and to prepare drugs for the treatment of pain diseases mediated by Nav1.8 such as of intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, primary pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, and cardiac arrhythmia, with broad application prospects.
A compound serving as a BTK inhibitor, a preparation method therefor, and a use thereof. The compound has a structure represented by formula I, or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer or a mixture thereof, or a pharmaceutically acceptable hydrate, solvent, or salt thereof, wherein A1, A2, A3, A4, A5 and A6 are each independently selected from C—R5 and N, and at least one of those is N; and M is selected from substituted or unsubstituted saturated or heterosaturated hydrocarbyl, substituted or unsubstituted unsaturated cyclic group or heterocyclyl, and substituted or unsubstituted monocyclic, bicyclic, or tricyclic aryl or heteroaryl. The provided BTK protein kinase inhibitor has strong inhibition for wild BTK and mutated BTK (C481S), has good pharmacokinetic properties, and has good application prospects.
A compound serving as a BTK inhibitor, a preparation method therefor, and a use thereof. The compound has a structure represented by formula I, or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer or a mixture thereof, or a pharmaceutically acceptable hydrate, solvent, or salt thereof, wherein A1, A2, A3, A4, A5 and A6 are each independently selected from C—R5 and N, and at least one of those is N; and M is selected from substituted or unsubstituted saturated or heterosaturated hydrocarbyl, substituted or unsubstituted unsaturated cyclic group or heterocyclyl, and substituted or unsubstituted monocyclic, bicyclic, or tricyclic aryl or heteroaryl. The provided BTK protein kinase inhibitor has strong inhibition for wild BTK and mutated BTK (C481S), has good pharmacokinetic properties, and has good application prospects.
Provided are a pyrrole derivative and a preparation method and use therefor. Said type of compound has obvious inhibition and blocking effects on DHODH, may be used as a DHODH specific inhibitor, may be used for preparing a drug for treating a disease caused by fungal infection, may also be used for preparing an agricultural fungicide, and has wide application prospects.
The present invention discloses a compound as a sodium channel regulator, and this type of compound can effectively inhibit and block the activity of Nav1.8 ion channel, a subtype of voltage-gated sodium channels, and can be used as a specific Nav1.8 inhibitor and to prepare drugs for the treatment of pain diseases mediated by Nav1.8 such as of intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, primary pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, and cardiac arrhythmia, with broad application prospects.
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 237/10 - Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
10.
BENZYLAMINE OR BENZYL ALCOHOL DERIVATIVE AND USE THEREOF
Disclosed are a compound as a sodium channel regulator and the use thereof. The compound has obvious inhibition and blocking effects on the activity of the voltage-gated sodium ion channel subtype Nav1.8 ion channel, and can be used as a Nav1.8 specific inhibitor, and can be used for the preparation of a drug for treating diseases mediated by Nav1.8, such as intestinal pain, neuropathic pain, musculoskeletal pain, acute pain, inflammatory pain, cancer pain, primary pain, multiple sclerosis, Charcot-Marie-Tooth syndrome, incontinence, and arrhythmia, and has broad application prospects.
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 237/10 - Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
The present invention provides a compound as a PAK4 inhibitor having a structure shown in formula I, or a tautomer, mesomer, racemate, enantiomer, diastereomer or a mixture thereof, or a pharmaceutically acceptable hydrate, solvate, or salt thereof. Experimental results show that the compound prepared in the present invention has high inhibitory activity and selectivity on PAK4 kinase, and moreover, the stability of liver microsomes and rat PK are also increased.
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 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
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 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 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 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 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 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 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
12345655 or N, and at least one of those is N; and M is selected from substituted or unsubstituted saturated or heterosaturated hydrocarbyl, substituted or unsubstituted unsaturated cyclic group or heterocyclyl, and substituted or unsubstituted monocyclic, bicyclic, or tricyclic aryl or heteroaryl. The provided BTK protein kinase inhibitor has strong inhibition for wild BTK and mutated BTK (C481S), has good pharmacokinetic properties, and has good application prospects.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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 31/519 - PyrimidinesHydrogenated 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 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 11/00 - Drugs for disorders of the respiratory system
A compound serving as a BTK inhibitor, a preparation method therefor, and a use thereof. The compound has a structure represented by formula I, or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer or a mixture thereof, or a pharmaceutically acceptable hydrate, solvent, or salt thereof, wherein A1, A2, A3, A4, A5, and A6 are each independently selected from C-R5 or N, and at least one of those is N; and M is selected from substituted or unsubstituted saturated or heterosaturated hydrocarbyl, substituted or unsubstituted unsaturated cyclic group or heterocyclyl, and substituted or unsubstituted monocyclic, bicyclic, or tricyclic aryl or heteroaryl. The provided BTK protein kinase inhibitor has strong inhibition for wild BTK and mutated BTK (C481S), has good pharmacokinetic properties, and has good application prospects.
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 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 35/02 - Antineoplastic agents specific for leukemia
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A compound as a BTK inhibitor or an HER2 inhibitor, a preparation method therefor, and a use thereof. The compound comprises a structure as shown in formula II or a tautomer, a mesomer, a racemate, an enantiomer, a diastereomer, or a mixture form thereof, and a pharmaceutically acceptable hydrate, a solvate, or salt. The BTK protein kinase inhibitor of the present invention has strong inhibitory activity on wild-type BTK or mutated BTK (C481S), and some of the compounds have high brain permeability; the HER2 inhibitor of the present invention has good HER2 kinase inhibitory activity and high blood-brain barrier transmittance; and the compound of the present invention has good pharmacokinetic properties and a good application prospect.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring 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 31/519 - PyrimidinesHydrogenated 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 37/06 - Immunosuppressants, e.g. drugs for graft rejection
A61P 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04 - Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 11/00 - Drugs for disorders of the respiratory system
patents
