RU2018117503A - ЗАМЕЩЕННЫЕ ИНДАЗОЛЬНЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ RORγТ И ИХ ПРИМЕНЕНИЕ - Google Patents
ЗАМЕЩЕННЫЕ ИНДАЗОЛЬНЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ RORγТ И ИХ ПРИМЕНЕНИЕ Download PDFInfo
- Publication number
- RU2018117503A RU2018117503A RU2018117503A RU2018117503A RU2018117503A RU 2018117503 A RU2018117503 A RU 2018117503A RU 2018117503 A RU2018117503 A RU 2018117503A RU 2018117503 A RU2018117503 A RU 2018117503A RU 2018117503 A RU2018117503 A RU 2018117503A
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- RU
- Russia
- Prior art keywords
- tetrahydro
- chloro
- carboxylic acid
- indazol
- cyclohex
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims 47
- 102000001691 Member 3 Group F Nuclear Receptor Subfamily 1 Human genes 0.000 title 1
- 108010029279 Member 3 Group F Nuclear Receptor Subfamily 1 Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- VUSWCWPCANWBFG-UHFFFAOYSA-N cyclohex-3-ene-1-carboxylic acid Chemical compound OC(=O)C1CCC=CC1 VUSWCWPCANWBFG-UHFFFAOYSA-N 0.000 claims 129
- 125000000217 alkyl group Chemical group 0.000 claims 67
- -1 2-chloro-6-cyclopropylbenzoyl Chemical group 0.000 claims 35
- 229910052736 halogen Inorganic materials 0.000 claims 23
- 150000002367 halogens Chemical class 0.000 claims 23
- 125000000623 heterocyclic group Chemical group 0.000 claims 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims 15
- 229910052757 nitrogen Inorganic materials 0.000 claims 14
- 125000004043 oxo group Chemical group O=* 0.000 claims 14
- 125000002619 bicyclic group Chemical group 0.000 claims 10
- 125000004122 cyclic group Chemical group 0.000 claims 10
- 238000000034 method Methods 0.000 claims 10
- 150000003839 salts Chemical class 0.000 claims 10
- 229910052799 carbon Inorganic materials 0.000 claims 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 7
- 208000023275 Autoimmune disease Diseases 0.000 claims 6
- 125000004429 atom Chemical group 0.000 claims 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 6
- 229910052760 oxygen Inorganic materials 0.000 claims 6
- 125000001424 substituent group Chemical group 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 5
- 208000035475 disorder Diseases 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 4
- 208000027866 inflammatory disease Diseases 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 229910052717 sulfur Inorganic materials 0.000 claims 4
- 201000004681 Psoriasis Diseases 0.000 claims 3
- 108091008773 RAR-related orphan receptors γ Proteins 0.000 claims 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 3
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 125000002393 azetidinyl group Chemical group 0.000 claims 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 201000008482 osteoarthritis Diseases 0.000 claims 2
- 125000003566 oxetanyl group Chemical group 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 238000002560 therapeutic procedure Methods 0.000 claims 2
- 208000015943 Coeliac disease Diseases 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 206010037549 Purpura Diseases 0.000 claims 1
- 241001672981 Purpura Species 0.000 claims 1
- 206010039710 Scleroderma Diseases 0.000 claims 1
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 208000006673 asthma Diseases 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 208000017760 chronic graft versus host disease Diseases 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 230000036566 epidermal hyperplasia Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 206010028417 myasthenia gravis Diseases 0.000 claims 1
- 208000023504 respiratory system disease Diseases 0.000 claims 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 230000003582 thrombocytopenic effect Effects 0.000 claims 1
- 230000001732 thrombotic effect Effects 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic 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
- C07D403/08—Heterocyclic 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—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 being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- C07D401/02—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
- C07D401/06—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- C07D401/02—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
- C07D401/12—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic 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
- C07D403/06—Heterocyclic 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 only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic 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
- C07D403/12—Heterocyclic 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—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
- C07D405/02—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
- C07D405/12—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic 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
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic 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
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562246921P | 2015-10-27 | 2015-10-27 | |
| US62/246,921 | 2015-10-27 | ||
| US201662372544P | 2016-08-09 | 2016-08-09 | |
| US62/372,544 | 2016-08-09 | ||
| PCT/US2016/059063 WO2017075182A1 (en) | 2015-10-27 | 2016-10-27 | Substituted indazole compounds as rorgammat inhibitors and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2018117503A true RU2018117503A (ru) | 2019-11-28 |
| RU2018117503A3 RU2018117503A3 (OSRAM) | 2020-02-04 |
Family
ID=58631831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018117503A RU2018117503A (ru) | 2015-10-27 | 2016-10-27 | ЗАМЕЩЕННЫЕ ИНДАЗОЛЬНЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ RORγТ И ИХ ПРИМЕНЕНИЕ |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US10287272B2 (OSRAM) |
| EP (1) | EP3368539B1 (OSRAM) |
| JP (1) | JP2018535958A (OSRAM) |
| KR (1) | KR20180070697A (OSRAM) |
| CN (1) | CN108431009A (OSRAM) |
| AU (1) | AU2016344115A1 (OSRAM) |
| CA (1) | CA3002850A1 (OSRAM) |
| IL (1) | IL258870A (OSRAM) |
| MX (1) | MX2018005004A (OSRAM) |
| RU (1) | RU2018117503A (OSRAM) |
| WO (1) | WO2017075182A1 (OSRAM) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9809561B2 (en) | 2013-12-20 | 2017-11-07 | Merck Sharp & Dohme Corp. | Tetrahydronaphthyridine, benzoxazine, aza-benzoxazine and related bicyclic compounds for inhibition of RORgamma activity and the treatment of disease |
| WO2017075182A1 (en) * | 2015-10-27 | 2017-05-04 | Merck Sharp & Dohme Corp. | Substituted indazole compounds as rorgammat inhibitors and uses thereof |
| WO2017075185A1 (en) | 2015-10-27 | 2017-05-04 | Merck Sharp & Dohme Corp. | Heteroaryl substituted benzoic acids as rorgammat inhibitors and uses thereof |
| CA3094988A1 (en) | 2018-03-30 | 2019-10-03 | Biotheryx, Inc. | Thienopyrimidinone compounds |
| WO2020229398A1 (de) | 2019-05-14 | 2020-11-19 | Bayer Aktiengesellschaft | (1-alkenyl)-substituierte pyrazole und triazole als schädlingsbekämpfungsmittel |
| WO2022140169A1 (en) * | 2020-12-22 | 2022-06-30 | Merck Sharp & Dohme Corp. | Preparation of tetrahydroindazole derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors |
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-
2016
- 2016-10-27 WO PCT/US2016/059063 patent/WO2017075182A1/en not_active Ceased
- 2016-10-27 AU AU2016344115A patent/AU2016344115A1/en not_active Abandoned
- 2016-10-27 JP JP2018521300A patent/JP2018535958A/ja not_active Ceased
- 2016-10-27 KR KR1020187014954A patent/KR20180070697A/ko not_active Withdrawn
- 2016-10-27 MX MX2018005004A patent/MX2018005004A/es unknown
- 2016-10-27 US US15/770,256 patent/US10287272B2/en active Active
- 2016-10-27 EP EP16860768.7A patent/EP3368539B1/en active Active
- 2016-10-27 CA CA3002850A patent/CA3002850A1/en not_active Abandoned
- 2016-10-27 CN CN201680076306.2A patent/CN108431009A/zh active Pending
- 2016-10-27 RU RU2018117503A patent/RU2018117503A/ru not_active Application Discontinuation
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2018
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2019
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| EP3368539A4 (en) | 2019-04-17 |
| EP3368539A1 (en) | 2018-09-05 |
| EP3368539B1 (en) | 2020-12-02 |
| US20180312489A1 (en) | 2018-11-01 |
| JP2018535958A (ja) | 2018-12-06 |
| CN108431009A (zh) | 2018-08-21 |
| MX2018005004A (es) | 2018-09-12 |
| KR20180070697A (ko) | 2018-06-26 |
| US10689369B2 (en) | 2020-06-23 |
| US10287272B2 (en) | 2019-05-14 |
| WO2017075182A1 (en) | 2017-05-04 |
| IL258870A (en) | 2018-06-28 |
| CA3002850A1 (en) | 2017-05-04 |
| AU2016344115A1 (en) | 2018-05-10 |
| US20190276438A1 (en) | 2019-09-12 |
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