CA2941824A1 - Amides d'acide phenylamino-oxazole-4-carboxylique substitues en tant qu'inhibiteurs de la kinase tyk2 - Google Patents
Amides d'acide phenylamino-oxazole-4-carboxylique substitues en tant qu'inhibiteurs de la kinase tyk2 Download PDFInfo
- Publication number
- CA2941824A1 CA2941824A1 CA2941824A CA2941824A CA2941824A1 CA 2941824 A1 CA2941824 A1 CA 2941824A1 CA 2941824 A CA2941824 A CA 2941824A CA 2941824 A CA2941824 A CA 2941824A CA 2941824 A1 CA2941824 A1 CA 2941824A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- oxazole
- disease
- phenylamino
- heterocyclic rings
- 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.)
- Granted
Links
- -1 phenylamino-oxazole-4-carboxylic acid amides Chemical class 0.000 title claims abstract description 52
- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 241
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 82
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 62
- 239000001257 hydrogen Substances 0.000 claims abstract description 62
- 150000003839 salts Chemical class 0.000 claims abstract description 50
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 39
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 38
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229910052731 fluorine Chemical group 0.000 claims abstract description 26
- 239000000460 chlorine Substances 0.000 claims abstract description 25
- 239000011737 fluorine Chemical group 0.000 claims abstract description 25
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 22
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 21
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 21
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 19
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001301 oxygen Substances 0.000 claims abstract description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 13
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims abstract description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 150000001408 amides Chemical class 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
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- 238000000034 method Methods 0.000 claims description 119
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 70
- 201000010099 disease Diseases 0.000 claims description 67
- 101000844245 Homo sapiens Non-receptor tyrosine-protein kinase TYK2 Proteins 0.000 claims description 61
- 102100032028 Non-receptor tyrosine-protein kinase TYK2 Human genes 0.000 claims description 60
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 54
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 53
- 108010010057 TYK2 Kinase Proteins 0.000 claims description 47
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- 125000001424 substituent group Chemical group 0.000 claims description 45
- 125000004423 acyloxy group Chemical group 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
- 230000002401 inhibitory effect Effects 0.000 claims description 30
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 29
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 28
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- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 25
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 24
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- 125000003282 alkyl amino group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- VAELWSLNTRVXQS-UHFFFAOYSA-N 1,3-oxazole-4-carboxamide Chemical compound NC(=O)C1=COC=N1 VAELWSLNTRVXQS-UHFFFAOYSA-N 0.000 claims description 19
- 230000005764 inhibitory process Effects 0.000 claims description 19
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 18
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
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- 229910052736 halogen Inorganic materials 0.000 claims description 6
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- 125000003302 alkenyloxy group Chemical group 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
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- 125000001544 thienyl group Chemical group 0.000 claims description 5
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- KUMWERTZYYEHSV-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-5-(4-methylsulfonylanilino)-1,3-oxazole-4-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=C(C(N)=O)N=C(C=2C(=CC=C(F)C=2)F)O1 KUMWERTZYYEHSV-UHFFFAOYSA-N 0.000 claims description 2
- LELIWIPWPFFQAG-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-5-[4-(2-hydroxyethylcarbamoyl)anilino]-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C=1N=C(C=2C(=CC=CC=2F)F)OC=1NC1=CC=C(C(=O)NCCO)C=C1 LELIWIPWPFFQAG-UHFFFAOYSA-N 0.000 claims description 2
- HLLHUBLRZHHTBY-UHFFFAOYSA-N 2-(2,6-difluorophenyl)-5-[4-(3-hydroxypropylcarbamoyl)anilino]-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C=1N=C(C=2C(=CC=CC=2F)F)OC=1NC1=CC=C(C(=O)NCCCO)C=C1 HLLHUBLRZHHTBY-UHFFFAOYSA-N 0.000 claims description 2
- BHDQJSFICYHNKA-UHFFFAOYSA-N 2-(2-chloro-6-fluorophenyl)-5-(4-methylsulfonylanilino)-1,3-oxazole-4-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=C(C(N)=O)N=C(C=2C(=CC=CC=2F)Cl)O1 BHDQJSFICYHNKA-UHFFFAOYSA-N 0.000 claims description 2
- PWKNMZKSSBJPFN-UHFFFAOYSA-N 5-(4-methylsulfonylanilino)-2-(2,4,6-trifluorophenyl)-1,3-oxazole-4-carboxamide Chemical compound C1=CC(S(=O)(=O)C)=CC=C1NC1=C(C(N)=O)N=C(C=2C(=CC(F)=CC=2F)F)O1 PWKNMZKSSBJPFN-UHFFFAOYSA-N 0.000 claims description 2
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- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical group [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 6
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- OLKSZFBBMNHFRV-CQSZACIVSA-N 2-(2,6-dichlorophenyl)-5-[4-[[(3r)-piperidin-3-yl]carbamoyl]anilino]-1,3-oxazole-4-carboxamide Chemical compound NC(=O)C=1N=C(C=2C(=CC=CC=2Cl)Cl)OC=1NC(C=C1)=CC=C1C(=O)N[C@@H]1CCCNC1 OLKSZFBBMNHFRV-CQSZACIVSA-N 0.000 claims 1
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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| PCT/EP2013/068198 WO2015032423A1 (fr) | 2013-09-03 | 2013-09-03 | Composés pharmaceutiques |
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| CA2941824A1 true CA2941824A1 (fr) | 2015-03-12 |
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| GB201617871D0 (en) | 2016-10-21 | 2016-12-07 | Sareum Limited | Pharmaceutical compounds |
| WO2019132654A1 (fr) * | 2017-12-27 | 2019-07-04 | Erasmus University Medical Center Rotterdam | Méthodes de traitement de la sarcoïdose |
| WO2020009566A1 (fr) * | 2018-07-04 | 2020-01-09 | Erasmus University Medical Center Rotterdam | Méthodes de traitement de la sarcoïdose |
| GB201816369D0 (en) * | 2018-10-08 | 2018-11-28 | Sareum Ltd | Pharmaceutical compounds |
| BR112021021809A2 (pt) | 2019-04-30 | 2022-01-04 | Celgene Corp | Terapias de combinação compreendendo os inibidores de apremilast e tyk2 |
| GB202005114D0 (en) | 2020-04-07 | 2020-05-20 | Sareum Ltd | Crystalline Forms of a Pharmaceutical Compound |
| EP3944859A1 (fr) | 2020-07-30 | 2022-02-02 | Assistance Publique Hôpitaux de Paris | Procédé de traitement des toxicités immunitaires induites par des inhibiteurs des points de contrôle immunitaire |
| KR20240070634A (ko) | 2021-09-30 | 2024-05-21 | 브리스톨-마이어스 스큅 컴퍼니 | Tyk2 억제제에 대한 반응성을 결정하는 방법 |
| CA3236262A1 (fr) | 2021-10-25 | 2023-05-04 | Isaac Marx | Agents de degradation de tyk2 et leurs utilisations |
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| GB1497536A (en) * | 1973-12-17 | 1978-01-12 | Lilly Industries Ltd | 2-acylaminooxazoles methods for their preparation and their use |
| ATE292118T1 (de) * | 1998-05-05 | 2005-04-15 | Hoffmann La Roche | Pyrazolderivative als p-38 map kinase inhibitoren |
| GB0709031D0 (en) * | 2007-05-10 | 2007-06-20 | Sareum Ltd | Pharmaceutical compounds |
| JP5478488B2 (ja) | 2007-06-20 | 2014-04-23 | メルク・シャープ・アンド・ドーム・コーポレーション | Ｊａｎｕｓキナーゼの阻害剤 |
| AU2009274454A1 (en) | 2008-04-21 | 2010-01-28 | Merck Sharp & Dohme Corp. | Inhibitors of janus kinases |
| US8344144B2 (en) | 2008-06-18 | 2013-01-01 | Merck Sharp & Dohme Corp. | Inhibitors of Janus kinases |
| WO2010005841A1 (fr) | 2008-07-09 | 2010-01-14 | Merck & Co., Inc. | Inhibiteurs des kinases janus |
| EP2166006A1 (fr) * | 2008-09-18 | 2010-03-24 | Dompe' S.P.A. | Acides 2-aryl-propioniques et dérivés et compositions pharmaceutiques les contenant |
| GB0820819D0 (en) * | 2008-11-13 | 2008-12-24 | Sareum Ltd | Pharmaceutical compounds |
| BR112012023382A2 (pt) | 2010-03-17 | 2018-05-15 | F Hoffmann La Roche Ag T | compostos, composições e métodos de uso de imidazopiridina. |
| EP2588105A1 (fr) | 2010-07-01 | 2013-05-08 | Cellzome Limited | Triazolopyridines en tant qu'inhibiteurs de tyk2 |
| RU2014118954A (ru) * | 2011-10-12 | 2015-11-20 | Эррэй Биофарма Инк. | 5,7-ЗАМЕЩЕННЫЕ-ИМИДАЗО[1,2-c]ПИРИМИДИНЫ |
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2015032423A1 (fr) | 2015-03-12 |
| SG11201601503SA (en) | 2016-03-30 |
| CN105793245B (zh) | 2018-03-20 |
| ZA201602047B (en) | 2020-12-23 |
| BR112016004723B1 (pt) | 2022-08-30 |
| KR102191084B1 (ko) | 2020-12-15 |
| AU2013399913B2 (en) | 2018-03-15 |
| CA2941824C (fr) | 2020-08-25 |
| CN105793245A (zh) | 2016-07-20 |
| JP2016529264A (ja) | 2016-09-23 |
| IL244380A0 (en) | 2016-04-21 |
| KR20160048883A (ko) | 2016-05-04 |
| MX2016002738A (es) | 2016-08-11 |
| JP6239118B2 (ja) | 2017-11-29 |
| IL244380B (en) | 2018-01-31 |
| RU2016111522A (ru) | 2017-10-09 |
| BR112016004723A2 (fr) | 2017-08-01 |
| MX369974B (es) | 2019-11-27 |
| AU2013399913A1 (en) | 2016-03-24 |
| RU2652795C2 (ru) | 2018-05-03 |
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