JP2020500192A5 - - Google Patents
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- Publication number
- JP2020500192A5 JP2020500192A5 JP2019526304A JP2019526304A JP2020500192A5 JP 2020500192 A5 JP2020500192 A5 JP 2020500192A5 JP 2019526304 A JP2019526304 A JP 2019526304A JP 2019526304 A JP2019526304 A JP 2019526304A JP 2020500192 A5 JP2020500192 A5 JP 2020500192A5
- Authority
- JP
- Japan
- Prior art keywords
- indole
- carboxamide
- fluorophenyl
- dioxide tetrahydrothiophene
- tetrahydrothiophene
- 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.)
- Ceased
Links
- -1 tetrahydrothiophene-3-yl Chemical group 0.000 claims 87
- 150000001875 compounds Chemical class 0.000 claims 14
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 10
- 125000005842 heteroatom Chemical group 0.000 claims 8
- 125000000623 heterocyclic group Chemical group 0.000 claims 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 7
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 6
- 150000003839 salts Chemical class 0.000 claims 6
- 201000001320 Atherosclerosis Diseases 0.000 claims 5
- 125000001072 heteroaryl group Chemical group 0.000 claims 5
- 125000005843 halogen group Chemical group 0.000 claims 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 4
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- GQRKMAWMERSXSW-KRWDZBQOSA-N 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl]indole-6-carboxamide Chemical compound ClC1=C(C=CC=C1)C1=CN(C2=CC(=CC=C12)C(=O)N[C@@H](C)C=1C=NC(=CC=1)C(F)(F)F)C1=CC=C(C=C1)F GQRKMAWMERSXSW-KRWDZBQOSA-N 0.000 claims 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 2
- 208000008589 Obesity Diseases 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 235000020824 obesity Nutrition 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- HRLSPXZZQRKSTK-UHFFFAOYSA-N 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-methoxypropan-2-yl)indole-6-carboxamide Chemical compound ClC1=C(C=CC=C1)C1=CN(C2=CC(=CC=C12)C(=O)NC(COC)C)C1=CC=C(C=C1)F HRLSPXZZQRKSTK-UHFFFAOYSA-N 0.000 claims 1
- GUTBRTWBNWPSNT-UHFFFAOYSA-N 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-methyl-1-morpholin-4-ylpropan-2-yl)indole-6-carboxamide Chemical compound ClC1=C(C=CC=C1)C1=CN(C2=CC(=CC=C12)C(=O)NC(CN1CCOCC1)(C)C)C1=CC=C(C=C1)F GUTBRTWBNWPSNT-UHFFFAOYSA-N 0.000 claims 1
- GQRKMAWMERSXSW-QGZVFWFLSA-N 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl]indole-6-carboxamide Chemical compound ClC1=C(C=CC=C1)C1=CN(C2=CC(=CC=C12)C(=O)N[C@H](C)C=1C=NC(=CC=1)C(F)(F)F)C1=CC=C(C=C1)F GQRKMAWMERSXSW-QGZVFWFLSA-N 0.000 claims 1
- BEDISZNVFNEWKM-RUZDIDTESA-N 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-2-hydroxy-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl]indole-6-carboxamide Chemical compound ClC1=C(C=CC=C1)C1=CN(C2=CC(=CC=C12)C(=O)N[C@H](CO)C=1C=NC(=CC=1)C(F)(F)F)C1=CC=C(C=C1)F BEDISZNVFNEWKM-RUZDIDTESA-N 0.000 claims 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- 102100035762 Diacylglycerol O-acyltransferase 2 Human genes 0.000 claims 1
- 206010019708 Hepatic steatosis Diseases 0.000 claims 1
- 101000930020 Homo sapiens Diacylglycerol O-acyltransferase 2 Proteins 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- 230000008485 antagonism Effects 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 230000007850 degeneration Effects 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002440 hepatic effect Effects 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000002950 monocyclic group Chemical group 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 230000004044 response Effects 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- 0 *c1*c*(*)c*1 Chemical compound *c1*c*(*)c*1 0.000 description 6
- YLGJKANHAQIYRJ-UHFFFAOYSA-N Fc1cnc(C2CCC2)nc1 Chemical compound Fc1cnc(C2CCC2)nc1 YLGJKANHAQIYRJ-UHFFFAOYSA-N 0.000 description 2
- KZNOGTSWLDQYBV-UHFFFAOYSA-N CC(C)(CC1)CS1(=O)=O Chemical compound CC(C)(CC1)CS1(=O)=O KZNOGTSWLDQYBV-UHFFFAOYSA-N 0.000 description 1
- ANDAJJIYWUHCGN-UHFFFAOYSA-N CC(CC1)=CS1(O)=O Chemical compound CC(CC1)=CS1(O)=O ANDAJJIYWUHCGN-UHFFFAOYSA-N 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662424106P | 2016-11-18 | 2016-11-18 | |
| US62/424,106 | 2016-11-18 | ||
| PCT/US2017/061226 WO2018093698A1 (en) | 2016-11-18 | 2017-11-13 | Indole derivatives useful as inhibitors of diacylglyceride o-acyltransferase 2 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2020500192A JP2020500192A (ja) | 2020-01-09 |
| JP2020500192A5 true JP2020500192A5 (enExample) | 2020-10-22 |
Family
ID=62146797
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019526304A Ceased JP2020500192A (ja) | 2016-11-18 | 2017-11-13 | ジアシルグリセリドｏ−アシルトランスフェラーゼ２の阻害薬として有用なインドール誘導体 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US10947222B2 (enExample) |
| EP (1) | EP3541376B1 (enExample) |
| JP (1) | JP2020500192A (enExample) |
| KR (1) | KR20190085035A (enExample) |
| CN (1) | CN109963561A (enExample) |
| AU (1) | AU2017360941A1 (enExample) |
| BR (1) | BR112019009731A2 (enExample) |
| CA (1) | CA3043206A1 (enExample) |
| MA (1) | MA46859A (enExample) |
| MX (1) | MX2019005679A (enExample) |
| RU (1) | RU2019117958A (enExample) |
| WO (1) | WO2018093698A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20230174521A1 (en) * | 2020-05-18 | 2023-06-08 | Merck Sharp & Dohme Llc | Novel diacylglyceride o-acyltransferase 2 inhibitors |
| US20240083861A1 (en) * | 2020-09-30 | 2024-03-14 | Fl2022-001, Inc. | Hsd17b13 inhibitors and uses thereof |
| AU2021356589A1 (en) * | 2020-10-08 | 2023-05-25 | Merck Sharp & Dohme Llc | Preparation of benzimidazolone derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors |
| KR102993831B1 (ko) * | 2020-10-08 | 2026-07-23 | 머크 샤프 앤드 돔 엘엘씨 | 신규 디아실글리세리드 o-아실트랜스퍼라제 2 억제제로서의 옥스인돌 유도체의 제조 |
| AU2021409234A1 (en) | 2020-12-22 | 2023-06-29 | Merck Sharp & Dohme Llc | Preparation of tetrahydroindazole derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors |
| AU2023400409A1 (en) | 2022-12-02 | 2025-06-26 | Merck Sharp & Dohme Llc | Preparation of fused azole derivatives as novel diacylglyceride o-acyltransferase 2 inhibitors |
| IL321907A (en) * | 2023-01-09 | 2025-09-01 | Univ Florida | pparg modulators |
| CN121591637B (zh) * | 2025-11-28 | 2026-07-17 | 广州医科大学 | 5-(苄基氨基甲酰基)-吲哚类化合物及其在制备防治糖尿病心肌病药物中的应用 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3841520A1 (de) | 1988-12-09 | 1990-06-13 | Hoechst Ag | Enzymhemmende harnstoffderivate von dipeptiden, verfahren zu ihrer herstellung, diese enthaltende mittel und ihre verwendung |
| US5104869A (en) | 1989-10-11 | 1992-04-14 | American Cyanamid Company | Renin inhibitors |
| US5114937A (en) | 1989-11-28 | 1992-05-19 | Warner-Lambert Company | Renin inhibiting nonpeptides |
| US5095119A (en) | 1990-03-08 | 1992-03-10 | American Home Products Corporation | Renin inhibitors |
| DE69819311T2 (de) | 1997-03-07 | 2004-07-29 | Metabasis Therapeutics Inc., San Diego | Neue benzimidazol inhibitoren der fructose-1,6-bisphosphatase |
| AU6691798A (en) | 1997-03-07 | 1998-09-22 | Metabasis Therapeutics, Inc. | Novel indole and azaindole inhibitors of fructose-1,6-bisphosphatase |
| WO1998039344A1 (en) | 1997-03-07 | 1998-09-11 | Metabasis Therapeutics, Inc. | Novel purine inhibitors of fructose-1,6-bisphosphatase |
| CZ297264B6 (cs) | 1998-09-09 | 2006-10-11 | Metabasis Therapeutics, Inc. | Nové heteroaromatické inhibitory fruktóza-1,6-bisfosfatázy |
| CA2415742A1 (en) | 2000-07-25 | 2002-01-31 | Merck & Co., Inc. | N-substituted indoles useful in the treatment of diabetes |
| US6852738B2 (en) | 2001-01-30 | 2005-02-08 | Merck & Co., Inc. | Acyl sulfamides for treatment of obesity, diabetes and lipid disorders |
| PE20030547A1 (es) * | 2001-09-24 | 2003-08-18 | Bayer Corp | Derivados de imidazol para el tratamiento de la obesidad |
| AR040241A1 (es) | 2002-06-10 | 2005-03-23 | Merck & Co Inc | Inhibidores de la 11-beta-hidroxiesteroide deshidrogrenasa 1 para el tratamiento de la diabetes obesidad y dislipidemia |
| WO2004019869A2 (en) | 2002-08-29 | 2004-03-11 | Merck & Co., Inc. | Indoles having anti-diabetic activity |
| CA2495943C (en) | 2002-08-29 | 2009-07-21 | Merck & Co., Inc. | Indoles having anti-diabetic activity |
| CA2512879A1 (en) | 2003-01-17 | 2004-08-12 | Soumya P. Sahoo | N-cyclohexylaminocarbonyl benzenesulfonamide derivatives |
| EA200700243A1 (ru) | 2004-07-14 | 2007-08-31 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Способы лечения гепатита с |
| US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
| WO2007084413A2 (en) | 2004-07-14 | 2007-07-26 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| WO2006117314A2 (en) | 2005-04-30 | 2006-11-09 | Boehringer Ingelheim International Gmbh | Novel piperidin- substituted indoles and their use as ccr-3 modulators |
| JP4847275B2 (ja) * | 2005-10-21 | 2011-12-28 | 田辺三菱製薬株式会社 | ピラゾロ［１，５−ａ］ピリミジン化合物 |
| JP2009523732A (ja) | 2006-01-13 | 2009-06-25 | ピーティーシー セラピューティクス，インコーポレーテッド | Ｃ型肝炎の治療方法 |
| US7514433B2 (en) | 2006-08-03 | 2009-04-07 | Hoffmann-La Roche Inc. | 1H-indole-6-yl-piperazin-1-yl-methanone derivatives |
| WO2008088692A2 (en) | 2007-01-12 | 2008-07-24 | Merck & Co., Inc. | Spirochromanon derivatives |
| US20100179173A1 (en) | 2007-06-28 | 2010-07-15 | Daniel Guay | Substituted fused pyrimidines as antagonists of gpr105 activity |
| EP2174343A1 (en) | 2007-06-28 | 2010-04-14 | Semiconductor Energy Laboratory Co, Ltd. | Manufacturing method of semiconductor device |
| US20110301079A1 (en) | 2007-09-21 | 2011-12-08 | Instituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Neuromedin u receptor agonists and uses thereof |
| WO2009058298A1 (en) | 2007-10-31 | 2009-05-07 | Merck & Co., Inc. | P2x3, receptor antagonists for treatment of pain |
| EP2215048B1 (en) | 2007-10-31 | 2015-10-28 | Merck Sharp & Dohme Corp. | P2x3 receptor antagonists for treatment of pain |
| AR070398A1 (es) | 2008-02-22 | 2010-03-31 | Gruenenthal Chemie | Derivados sustituidos de indol |
| CA2741666C (en) | 2008-10-31 | 2017-04-11 | Merck Sharp & Dohme Corp. | P2x3, receptor antagonists for treatment of pain |
| JP2012520887A (ja) | 2009-03-18 | 2012-09-10 | シェーリング コーポレイション | ジアシルグリセロールアシルトランスフェラーゼの阻害剤としての二環式化合物 |
| JP2012521429A (ja) * | 2009-03-23 | 2012-09-13 | メルク・シャープ・エンド・ドーム・コーポレイション | 疼痛治療用のｐ２ｘ３受容体アンタゴニスト |
| US8946231B2 (en) | 2009-03-23 | 2015-02-03 | Merck Sharp & Dohme Corp. | P2X3, receptor antagonists for treatment of pain |
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| WO2012150784A2 (ko) | 2011-05-03 | 2012-11-08 | 한국생명공학연구원 | 신규한 인돌 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 대사성 질환의 예방 또는 치료용 약학적 조성물 |
| EP3492474B1 (en) * | 2012-11-23 | 2021-08-11 | GlaxoSmithKline LLC | Intermediates used in the production of diacylglycerol acyltransferase inhibitors |
| US10568876B2 (en) | 2014-09-05 | 2020-02-25 | Merck Sharp & Dohme Corp. | Tetrahydroisoquinoline derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2 |
| EP3188730B1 (en) | 2014-09-05 | 2019-05-01 | Merck Sharp & Dohme Corp. | Tetrahydroisoquinoline derivatives useful as inhibitors of diacylglyceride o-acyltransferase 2 |
| WO2016036638A1 (en) | 2014-09-05 | 2016-03-10 | Merck Sharp & Dohme Corp. | Isoquinoline derivatives useful as inhibitors of diacylglyceride o-acyltransferase 2 |
| CA2982267C (en) | 2015-05-20 | 2019-11-12 | Eli Lilly And Company | Novel dgat2 inhibitors |
-
2017
- 2017-11-13 CN CN201780071481.7A patent/CN109963561A/zh active Pending
- 2017-11-13 EP EP17871875.5A patent/EP3541376B1/en active Active
- 2017-11-13 BR BR112019009731A patent/BR112019009731A2/pt not_active IP Right Cessation
- 2017-11-13 JP JP2019526304A patent/JP2020500192A/ja not_active Ceased
- 2017-11-13 CA CA3043206A patent/CA3043206A1/en not_active Abandoned
- 2017-11-13 US US16/461,880 patent/US10947222B2/en active Active
- 2017-11-13 KR KR1020197016982A patent/KR20190085035A/ko not_active Withdrawn
- 2017-11-13 MA MA046859A patent/MA46859A/fr unknown
- 2017-11-13 MX MX2019005679A patent/MX2019005679A/es unknown
- 2017-11-13 AU AU2017360941A patent/AU2017360941A1/en not_active Abandoned
- 2017-11-13 WO PCT/US2017/061226 patent/WO2018093698A1/en not_active Ceased
- 2017-11-13 RU RU2019117958A patent/RU2019117958A/ru unknown