TW201247627A - Novel bicyclic nitrogen containing heteroaryl TGR5 receptor modulators - Google Patents
Novel bicyclic nitrogen containing heteroaryl TGR5 receptor modulators Download PDFInfo
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- TW201247627A TW201247627A TW101115262A TW101115262A TW201247627A TW 201247627 A TW201247627 A TW 201247627A TW 101115262 A TW101115262 A TW 101115262A TW 101115262 A TW101115262 A TW 101115262A TW 201247627 A TW201247627 A TW 201247627A
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- Prior art keywords
- alkyl
- group
- aryl
- cycloalkyl
- hydrogen
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- RONWGALEIBILOG-VMJVVOMYSA-N quinine sulfate Chemical compound [H+].[H+].[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 RONWGALEIBILOG-VMJVVOMYSA-N 0.000 description 1
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- IXBPPZBJIFNGJJ-UHFFFAOYSA-N sodium;cyanoiminomethylideneazanide Chemical compound [Na+].N#C[N-]C#N IXBPPZBJIFNGJJ-UHFFFAOYSA-N 0.000 description 1
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- DOMTZTVJNZKUNX-UHFFFAOYSA-N tert-butyl 3-aminopropanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)CCN DOMTZTVJNZKUNX-UHFFFAOYSA-N 0.000 description 1
- IZUZIVIUDTZPFE-UHFFFAOYSA-N tert-butyl decanoate Chemical compound CCCCCCCCCC(=O)OC(C)(C)C IZUZIVIUDTZPFE-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D401/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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| PE20190710A1 (es) | 2014-10-24 | 2019-05-17 | Bristol Myers Squibb Co | Compuestos de indol carboxamida utiles como inhibidores de cinasas |
| US10023534B2 (en) | 2014-10-24 | 2018-07-17 | Bristol-Myers Squibb Company | Carbazole and tetrahydrocarbazole compounds useful as inhibitors of BTK |
| WO2018005794A2 (en) * | 2016-07-01 | 2018-01-04 | Venenum Biodesign Llc | Novel non-systemic tgr5 agonists |
| TW201840542A (zh) * | 2017-03-22 | 2018-11-16 | 瑞士商先正達合夥公司 | 殺有害生物活性環丙基甲基醯胺衍生物 |
| JP2022552655A (ja) | 2019-10-07 | 2022-12-19 | キャリーオペ,インク. | Gpr119アゴニスト |
| CA3166630A1 (en) | 2020-01-03 | 2021-07-08 | Berg Llc | Polycyclic amides as ube2k modulators for treating cancer |
| TW202140440A (zh) | 2020-02-28 | 2021-11-01 | 美商克力歐普股份有限公司 | Gpr40激動劑 |
| AU2021275038A1 (en) | 2020-05-19 | 2022-12-22 | Kallyope, Inc. | AMPK activators |
| CA3183575A1 (en) | 2020-06-26 | 2021-12-30 | Iyassu Sebhat | Ampk activators |
| CN114199812A (zh) * | 2021-12-28 | 2022-03-18 | 南通联亚药业有限公司 | 一种盐酸美金刚缓释制剂中盐酸美金刚的检测方法 |
| EP4493551A1 (en) | 2022-03-14 | 2025-01-22 | Slap Pharmaceuticals LLC | Multicyclic compounds |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991005549A1 (en) * | 1989-10-20 | 1991-05-02 | Otsuka Pharmaceutical Co., Ltd. | Benzoheterocyclic compounds |
| GB9307527D0 (en) * | 1993-04-13 | 1993-06-02 | Fujisawa Pharmaceutical Co | New venzamide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
| JP3362494B2 (ja) | 1994-03-01 | 2003-01-07 | 三菱ウェルファーマ株式会社 | ベンゾオキサジン化合物 |
| JP2006063064A (ja) * | 2004-07-27 | 2006-03-09 | Takeda Chem Ind Ltd | 受容体作動剤 |
| US7989461B2 (en) * | 2005-12-23 | 2011-08-02 | Amgen Inc. | Substituted quinazolinamine compounds for the treatment of cancer |
| WO2008067222A1 (en) | 2006-11-28 | 2008-06-05 | Kalypsys, Inc. | Heterocyclic modulators of tgr5 |
| WO2008067219A2 (en) | 2006-11-29 | 2008-06-05 | Kalypsys, Inc. | Quinazolinone modulators of tgr5 |
| US20080221161A1 (en) | 2007-02-09 | 2008-09-11 | Kalypsys, Inc. | Heterocyclic modulators of tgr5 for treatment of disease |
| WO2009026241A1 (en) | 2007-08-23 | 2009-02-26 | Kalypsys, Inc. | Heterocyclic modulators of tgr5 |
| US20110136788A1 (en) * | 2008-08-07 | 2011-06-09 | Minoru Maruyama | Therapeutic agent for irritable bowel syndrome |
| WO2010016846A1 (en) | 2008-08-08 | 2010-02-11 | Kalypsys, Inc. | Heterocyclic modulators of tgr5 for treatment of disease |
| PE20110574A1 (es) | 2008-10-29 | 2011-08-11 | Hoffmann La Roche | Derivados de fenilamida y de piridilamida como agonistas de gpbar1 |
| JP5639073B2 (ja) | 2008-11-19 | 2014-12-10 | インターセプト ファーマシューティカルズ, インコーポレイテッド | Tgr5モジュレーターおよびその使用方法 |
| JP2012517479A (ja) | 2009-02-12 | 2012-08-02 | エグゼリクシス, インコーポレイテッド | 糖尿病および肥満の処置においてtgr5アゴニストとして使用するためのトリアゾールおよびイミダゾール誘導体 |
| US8637507B2 (en) * | 2009-03-18 | 2014-01-28 | Merck Sharp & Dohme Corp. | Bicyclic compounds as inhibitors of diacylglycerol acyltransferase |
| US8846739B2 (en) | 2009-12-11 | 2014-09-30 | Exelixis Patent Company Llc | TGR5 agonists |
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- 2012-04-27 US US14/113,593 patent/US9062028B2/en active Active
- 2012-04-27 EP EP12723982.0A patent/EP2702042A1/en not_active Withdrawn
- 2012-04-27 CN CN201280031836.7A patent/CN103619817A/zh active Pending
- 2012-04-27 WO PCT/US2012/035327 patent/WO2012149236A1/en not_active Ceased
- 2012-04-27 TW TW101115262A patent/TW201247627A/zh unknown
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|---|---|
| EP2702042A1 (en) | 2014-03-05 |
| US20140080788A1 (en) | 2014-03-20 |
| WO2012149236A1 (en) | 2012-11-01 |
| US9062028B2 (en) | 2015-06-23 |
| CN103619817A (zh) | 2014-03-05 |
| JP2014518853A (ja) | 2014-08-07 |
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