CN115605463B - 用于治疗疾病的受体相互作用蛋白激酶i的抑制剂 - Google Patents

用于治疗疾病的受体相互作用蛋白激酶i的抑制剂 Download PDF

Info

Publication number
CN115605463B
CN115605463B CN202080067791.3A CN202080067791A CN115605463B CN 115605463 B CN115605463 B CN 115605463B CN 202080067791 A CN202080067791 A CN 202080067791A CN 115605463 B CN115605463 B CN 115605463B
Authority
CN
China
Prior art keywords
compound
mmol
alkyl
methyl
bicyclo
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202080067791.3A
Other languages
English (en)
Chinese (zh)
Other versions
CN115605463A (zh
Inventor
R·刘易斯
M·汉密尔顿
W·雷
F·阿尔瓦雷斯
D·菲芬格
N·雷纳
J·克罗斯
S·K·V·拉马斯瓦米
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Texas System
Original Assignee
University of Texas System
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by University of Texas System filed Critical University of Texas System
Publication of CN115605463A publication Critical patent/CN115605463A/zh
Application granted granted Critical
Publication of CN115605463B publication Critical patent/CN115605463B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/4015Heterocyclic 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 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/4025Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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 being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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 being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • A61K31/41551,2-Diazoles non condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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 being nitrogen, e.g. tetrazole
    • A61K31/4151,2-Diazoles
    • A61K31/4161,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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 being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41841,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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 being nitrogen, e.g. tetrazole
    • A61K31/41921,2,3-Triazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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 being nitrogen, e.g. tetrazole
    • A61K31/4245Oxadiazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic 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 being nitrogen, e.g. tetrazole
    • A61K31/425Thiazoles
    • A61K31/427Thiazoles not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/437Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439Non 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56Benzopyrazoles; Hydrogenated benzopyrazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-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
    • C07D241/24Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/08Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/10Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/08Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/10Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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 C07D415/00
    • C07D417/14Heterocyclic 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 C07D415/00 containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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 C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic 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 C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Ophthalmology & Optometry (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN202080067791.3A 2019-09-27 2020-09-25 用于治疗疾病的受体相互作用蛋白激酶i的抑制剂 Active CN115605463B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962907146P 2019-09-27 2019-09-27
US62/907,146 2019-09-27
PCT/US2020/052789 WO2021062199A1 (en) 2019-09-27 2020-09-25 Inhibitors of receptor interacting protein kinase i for the treatment of disease

Publications (2)

Publication Number Publication Date
CN115605463A CN115605463A (zh) 2023-01-13
CN115605463B true CN115605463B (zh) 2024-08-09

Family

ID=75162965

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202080067791.3A Active CN115605463B (zh) 2019-09-27 2020-09-25 用于治疗疾病的受体相互作用蛋白激酶i的抑制剂

Country Status (11)

Country Link
US (3) US11753381B2 (enExample)
EP (1) EP4034530A4 (enExample)
JP (2) JP7802655B2 (enExample)
KR (1) KR20220072857A (enExample)
CN (1) CN115605463B (enExample)
AU (1) AU2020353663B2 (enExample)
BR (1) BR112022005627A2 (enExample)
CA (1) CA3155259A1 (enExample)
IL (1) IL291665B2 (enExample)
MX (1) MX2022003671A (enExample)
WO (1) WO2021062199A1 (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021046515A1 (en) 2019-09-06 2021-03-11 Board Of Regents, The University Of Texas System Inhibitors of receptor interacting protein kinase i for the treatment of disease
IL291665B2 (en) 2019-09-27 2025-07-01 Univ Texas Inhibitors of receptor interacting protein kinase i for the treatment of disease
BR112022010082A2 (pt) 2019-11-26 2022-08-30 Univ Texas Composto de fórmula estrutural i ou sal do mesmo, composição farmacêutica, uso do composto e uso da composição farmacêutica
EP4294798A1 (en) * 2021-02-19 2023-12-27 Kalvista Pharmaceuticals Limited Factor xiia inhibitors
CN116444437B (zh) * 2023-03-08 2025-09-16 曲靖师范学院 抗癌医药达洛鲁胺的合成方法
CN121487930A (zh) * 2023-05-10 2026-02-06 建新公司 作为ripk1抑制剂的异噁唑烷及其用途
CN121079291A (zh) * 2023-05-10 2025-12-05 建新公司 作为ripk1抑制剂的异噁唑烷及其使用
WO2025165774A1 (en) * 2024-02-01 2025-08-07 Board Of Regents, The University Of Texas System Inhibitors of receptor interacting protein kinase i for the treatment of disease
WO2026001865A1 (en) * 2024-06-24 2026-01-02 Sironax Ltd. Rip1 modulators, preparations, and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106999451A (zh) * 2014-09-17 2017-08-01 卡利拉制药公司 双环化合物

Family Cites Families (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU778393B2 (en) 1999-05-12 2004-12-02 Ortho-Mcneil Pharmaceutical, Inc. Pyrazole carboxamides useful for the treatment of obesity and other disorders
JP2012513481A (ja) 2008-12-23 2012-06-14 プレジデント アンド フェロウズ オブ ハーバード カレッジ ネクロトーシスの小分子阻害剤
EP2421834A1 (en) 2009-04-24 2012-02-29 Glaxo Group Limited Pyrazole and triazole carboxamides as crac channel inhibitors
US8987275B2 (en) 2010-03-16 2015-03-24 Dana-Farber Cancer Institute, Inc. Indazole compounds and their uses
US9643977B2 (en) 2011-03-11 2017-05-09 President And Fellows Of Harvard College Necroptosis inhibitors and methods of use therefor
EP2739143B1 (en) 2011-08-05 2018-07-11 Gary A. Flynn Preparation and methods of use for ortho-aryl 5- membered heteroaryl-carboxamide containing multi-targeted kinase inhibitors
CN102643268B (zh) 2011-12-30 2014-05-21 沈阳药科大学 喹啉类及噌啉类化合物及其应用
DK2810937T3 (en) 2012-01-31 2017-03-13 Daiichi Sankyo Co Ltd PYRIDONE DERIVATIVES
TWI637951B (zh) 2013-02-15 2018-10-11 英商葛蘭素史克智慧財產發展有限公司 作為激酶抑制劑之雜環醯胺類
KR20150118158A (ko) 2013-02-22 2015-10-21 머크 샤프 앤드 돔 코포레이션 항당뇨병 비시클릭 화합물
SI3030549T1 (sl) 2013-09-12 2019-08-30 Janssen Biopharma, Inc. Spojine piridazinona in njihove uporabe
WO2015199206A1 (ja) * 2014-06-27 2015-12-30 塩野義製薬株式会社 Trpv4阻害活性を有する6員環誘導体
CN106573006A (zh) 2014-08-21 2017-04-19 葛兰素史密斯克莱知识产权发展有限公司 作为药物的rip1激酶抑制剂杂环酰胺
EP3224245B1 (en) * 2014-12-24 2018-09-12 National Institute Of Biological Sciences, Beijing Necrosis inhibitors
ES2769031T3 (es) * 2015-03-20 2020-06-24 Pfizer Agentes citotóxicos bifuncionales que contienen el farmacóforo cti
TWI730959B (zh) * 2015-05-19 2021-06-21 英商葛蘭素史克智慧財產發展有限公司 作為激酶抑制劑之雜環醯胺
EP3317269B1 (en) 2015-07-02 2022-09-21 F. Hoffmann-La Roche AG Bicyclic lactams as receptor-interacting protein-1 (rip1) kinase inhibitors for treating e.g. inflammatory diseases
AU2016340527B2 (en) 2015-10-23 2020-09-17 Takeda Pharmaceutical Company Limited Heterocyclic compound
WO2017096301A1 (en) * 2015-12-04 2017-06-08 Denali Therapeutics Inc. Isoxazolidine derived inhibitors of receptor interacting protein kinase 1 (ripk 1)
IL287136B2 (en) 2016-02-05 2023-09-01 Denali Therapeutics Inc Receptor inhibitors - interacting with protein kinase 1
CN109071409B (zh) * 2016-03-14 2021-09-17 斯帕罗化学股份公司 制备取代的双环[1 1 1]戊烷的方法
US10980806B2 (en) * 2016-03-24 2021-04-20 University of Pittsburgh—of the Commonwealth System of Higher Education Small molecule inhibitors of the nuclear translocation of androgen receptor for the treatment of castration-resistant prostate cancer
CN105785659B (zh) * 2016-05-20 2018-07-10 深圳市华星光电技术有限公司 含功能化石墨烯层的液晶面板结构及功能化石墨烯膜的制备方法
WO2018073193A1 (en) 2016-10-17 2018-04-26 F. Hoffmann-La Roche Ag Bicyclic pyridone lactams and methods of use thereof
US11071721B2 (en) 2016-12-02 2021-07-27 Genentech, Inc. Bicyclic amide compounds and methods of use thereof
KR20190087622A (ko) * 2016-12-08 2019-07-24 보드 오브 리전츠 더 유니버시티 오브 텍사스 시스템 질환 치료를 위한 이중 류신 지퍼 (dlk) 키나아제의 바이시클로[1.1.1]펜탄 억제제
JP7208137B2 (ja) 2016-12-09 2023-01-18 デナリ セラピューティクス インコーポレイテッド 化合物、組成物および方法
US11072607B2 (en) 2016-12-16 2021-07-27 Genentech, Inc. Inhibitors of RIP1 kinase and methods of use thereof
US20200062735A1 (en) 2017-02-27 2020-02-27 Glaxosmithkline Intellectual Property Development Limited Heterocyclic amides as kinase inhibitors
CA3063934A1 (en) * 2017-05-17 2018-11-22 Denali Therapeutics Inc. Kinase inhibitors and uses thereof
WO2019034178A1 (zh) * 2017-08-18 2019-02-21 四川百利药业有限责任公司 一种dna毒性二聚体化合物
IL272875B2 (en) * 2017-09-11 2023-10-01 Recurium Ip Holdings Llc Continuous flow processes for the preparation of bicyclic compounds
AR114136A1 (es) * 2017-10-10 2020-07-29 Hoffmann La Roche Compuestos heterocíclicos
EP3704125B1 (en) * 2017-11-02 2026-03-11 Calico Life Sciences LLC Modulators of the integrated stress pathway
UY37956A (es) * 2017-11-02 2019-05-31 Abbvie Inc Moduladores de la vía de estrés integrada
EP3494994A1 (en) 2017-12-07 2019-06-12 Universität zu Köln Combinations of ripk1- and ikk-inhibitors for the prevention or treatment of immune diseases
WO2019204537A1 (en) 2018-04-20 2019-10-24 Genentech, Inc. N-[4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-5,6-dihydro-4h-pyrrolo[1,2-b]pyrazol e-2-carboxamide derivatives and related compounds as rip1 kinase inhibitors for treating e.g. irritable bowel syndrome (ibs)
HRP20231381T1 (hr) 2018-05-03 2024-03-01 Rigel Pharmaceuticals, Inc. Spojevi inhibitori rip1 i postupci za njihovo dobivanje i upotrebu
MD3788045T2 (ro) 2018-05-03 2023-09-30 Rigel Pharmaceuticals Inc Compuși inhibitori ai RIP1 și procedee de obţinere și utilizare a acestora
WO2019224773A1 (en) * 2018-05-23 2019-11-28 Glaxosmithkline Intellectual Property Development Limited Heterocyclic amides as rip1 kinase inhibitors
WO2021046515A1 (en) 2019-09-06 2021-03-11 Board Of Regents, The University Of Texas System Inhibitors of receptor interacting protein kinase i for the treatment of disease
IL291665B2 (en) 2019-09-27 2025-07-01 Univ Texas Inhibitors of receptor interacting protein kinase i for the treatment of disease
US11560366B2 (en) * 2019-10-21 2023-01-24 Board Of Regents, The University Of Texas System Bicyclo[1.1.1]pentane inhibitors of dual leucine zipper (DLK) kinase for the treatment of disease
BR112022010082A2 (pt) 2019-11-26 2022-08-30 Univ Texas Composto de fórmula estrutural i ou sal do mesmo, composição farmacêutica, uso do composto e uso da composição farmacêutica
CA3169099A1 (en) 2020-02-28 2021-09-02 Board Of Regents, The University Of Texas System Inhibitors of receptor interacting protein kinase i for the treatment of disease

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106999451A (zh) * 2014-09-17 2017-08-01 卡利拉制药公司 双环化合物

Also Published As

Publication number Publication date
WO2021062199A1 (en) 2021-04-01
AU2020353663B2 (en) 2025-11-27
CN115605463A (zh) 2023-01-13
EP4034530A4 (en) 2023-09-06
US12286406B2 (en) 2025-04-29
US20210094921A1 (en) 2021-04-01
IL291665B1 (en) 2025-03-01
BR112022005627A2 (pt) 2022-07-12
AU2020353663A1 (en) 2022-04-07
IL291665B2 (en) 2025-07-01
US11753381B2 (en) 2023-09-12
CA3155259A1 (en) 2021-04-01
JP2022550099A (ja) 2022-11-30
US20240199554A1 (en) 2024-06-20
EP4034530A1 (en) 2022-08-03
US20250214942A1 (en) 2025-07-03
JP7802655B2 (ja) 2026-01-20
KR20220072857A (ko) 2022-06-02
IL291665A (en) 2022-05-01
MX2022003671A (es) 2022-04-25
JP2025138749A (ja) 2025-09-25

Similar Documents

Publication Publication Date Title
CN115605463B (zh) 用于治疗疾病的受体相互作用蛋白激酶i的抑制剂
CN112351780B (zh) Ptpn11的取代的杂环抑制剂
CA2890876C (en) N-pyrrolidinyl, n'-pyrazolyl- urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
US11718612B2 (en) Inhibitors of receptor interacting protein kinase I for the treatment of disease
CN108602776B (zh) 用作irak抑制剂的杂芳基化合物及其用途
JP7752125B2 (ja) 疾患の処置のための受容体相互作用プロテインキナーゼiの阻害剤
RS61012B1 (sr) Aromatični derivati sulfonamida
WO2014078372A1 (en) Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors
CN114981248A (zh) 用于治疗疾病的受体相互作用蛋白激酶i的抑制剂
EA046365B1 (ru) Ингибиторы взаимодействующей с рецептором протеинкиназы i для лечения заболевания
JP6258508B2 (ja) 新規のイミダゾリジン−2,4−ジオン誘導体
CA3022793C (en) Aromatic sulfonamide derivatives
WO2022192527A1 (en) Ethanediamine-heterocycle derivatives as inhibitors of protein arginine methyltransferases
HK40004540B (en) N-pyrrolidinyl, n’-pyrazolyl- urea compounds as trka kinase inhibitors
HK40004540A (en) N-pyrrolidinyl, n’-pyrazolyl- urea compounds as trka kinase inhibitors

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant