TWI547479B - （羥基烷基）吡咯衍生物之阻轉異構體 - Google Patents
（羥基烷基）吡咯衍生物之阻轉異構體 Download PDFInfo
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- TWI547479B TWI547479B TW098134174A TW98134174A TWI547479B TW I547479 B TWI547479 B TW I547479B TW 098134174 A TW098134174 A TW 098134174A TW 98134174 A TW98134174 A TW 98134174A TW I547479 B TWI547479 B TW I547479B
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- Prior art keywords
- phenyl
- atropisomer
- methyl
- compound
- pyrrole
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- 125000002768 hydroxyalkyl group Chemical group 0.000 title description 4
- 150000003233 pyrroles Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 106
- 239000000203 mixture Substances 0.000 claims description 42
- -1 1-[2-hydroxy-1-methylpropyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide Chemical compound 0.000 claims description 26
- 230000000694 effects Effects 0.000 claims description 20
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 19
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- 208000033679 diabetic kidney disease Diseases 0.000 claims description 19
- 208000017169 kidney disease Diseases 0.000 claims description 18
- 102000003979 Mineralocorticoid Receptors Human genes 0.000 claims description 17
- 108090000375 Mineralocorticoid Receptors Proteins 0.000 claims description 17
- 206010019280 Heart failures Diseases 0.000 claims description 14
- 229940126585 therapeutic drug Drugs 0.000 claims description 13
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 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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- 229940083712 aldosterone antagonist Drugs 0.000 claims description 10
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- 150000003839 salts Chemical class 0.000 claims description 10
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- 238000011282 treatment Methods 0.000 claims description 7
- AHFINSWGYAZBOZ-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)benzaldehyde Chemical group FC(F)(F)C1=CC(Cl)=CC=C1C=O AHFINSWGYAZBOZ-UHFFFAOYSA-N 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
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- RNOVGJWJVRESAA-UHFFFAOYSA-N 4-fluoro-2-(trifluoromethyl)phenol Chemical group OC1=CC=C(F)C=C1C(F)(F)F RNOVGJWJVRESAA-UHFFFAOYSA-N 0.000 claims description 4
- RKOXRANVRDCFQL-CABCVRRESA-N 5-[4-fluoro-2-(trifluoromethyl)phenyl]-1-[(2r,3s)-3-hydroxybutan-2-yl]-4-methyl-n-(4-methylsulfonylphenyl)pyrrole-3-carboxamide Chemical compound CC1=C(C=2C(=CC(F)=CC=2)C(F)(F)F)N([C@H](C)[C@@H](O)C)C=C1C(=O)NC1=CC=C(S(C)(=O)=O)C=C1 RKOXRANVRDCFQL-CABCVRRESA-N 0.000 claims description 4
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- AAJDXRXNKJLUSF-UHFFFAOYSA-N 1-(3-hydroxybutan-2-yl)-4-methyl-n-(4-methylsulfonylphenyl)-5-[2-(trifluoromethyl)phenyl]pyrrole-3-carboxamide Chemical compound CC1=C(C=2C(=CC=CC=2)C(F)(F)F)N(C(C)C(O)C)C=C1C(=O)NC1=CC=C(S(C)(=O)=O)C=C1 AAJDXRXNKJLUSF-UHFFFAOYSA-N 0.000 claims description 3
- AAJDXRXNKJLUSF-CVEARBPZSA-N 1-[(2r,3s)-3-hydroxybutan-2-yl]-4-methyl-n-(4-methylsulfonylphenyl)-5-[2-(trifluoromethyl)phenyl]pyrrole-3-carboxamide Chemical compound CC1=C(C=2C(=CC=CC=2)C(F)(F)F)N([C@H](C)[C@@H](O)C)C=C1C(=O)NC1=CC=C(S(C)(=O)=O)C=C1 AAJDXRXNKJLUSF-CVEARBPZSA-N 0.000 claims description 3
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- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 claims 1
- 229960000396 atropine Drugs 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 108091008039 hormone receptors Proteins 0.000 claims 1
- 239000002395 mineralocorticoid Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 101
- 235000019439 ethyl acetate Nutrition 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 27
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- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
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- 238000000034 method Methods 0.000 description 16
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 14
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 125000001309 chloro group Chemical group Cl* 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 230000000069 prophylactic effect Effects 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
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Classifications
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- C07D207/34—Heterocyclic 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 two 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
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic 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
- C07D207/30—Heterocyclic 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 two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic 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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—Heterocyclic 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 two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10371508P | 2008-10-08 | 2008-10-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201028377A TW201028377A (en) | 2010-08-01 |
| TWI547479B true TWI547479B (zh) | 2016-09-01 |
Family
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Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW098134174A TWI547479B (zh) | 2008-10-08 | 2009-10-08 | （羥基烷基）吡咯衍生物之阻轉異構體 |
| TW104142529A TWI593674B (zh) | 2008-10-08 | 2009-10-08 | 製造（羥基烷基）吡咯衍生物之方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW104142529A TWI593674B (zh) | 2008-10-08 | 2009-10-08 | 製造（羥基烷基）吡咯衍生物之方法 |
Country Status (12)
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|---|---|
| US (1) | US8487117B2 (enExample) |
| EP (1) | EP2349997B1 (enExample) |
| JP (2) | JP5767586B2 (enExample) |
| KR (1) | KR101643285B1 (enExample) |
| CN (1) | CN102186817B (enExample) |
| AU (1) | AU2009302371B2 (enExample) |
| BR (1) | BRPI0920459B1 (enExample) |
| CA (1) | CA2736923C (enExample) |
| ES (1) | ES2547697T3 (enExample) |
| IL (1) | IL212170A (enExample) |
| TW (2) | TWI547479B (enExample) |
| WO (1) | WO2010042622A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUE037007T2 (hu) * | 2013-08-27 | 2018-08-28 | Daiichi Sankyo Co Ltd | Eljárás pirrol származék elõállítására és annak intermediere |
| AU2020371836B2 (en) * | 2019-10-25 | 2026-01-29 | Sunshine Lake Pharma Co., Ltd. | Pyrrole amide compound and use thereof |
| EP4317133B1 (en) * | 2021-03-30 | 2026-04-15 | Sunshine Lake Pharma Co., Ltd. | Crystalline form of pyrrole amide compound, preparation method therefor and use thereof |
| CN115784961B (zh) * | 2021-09-10 | 2026-03-31 | 上海鼎雅药物化学科技有限公司 | 埃沙西林酮及其中间体的合成方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006012642A2 (en) * | 2004-07-30 | 2006-02-02 | Exelixis, Inc. | Pyrrole derivatives as pharmaceutical agents |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI444185B (zh) * | 2007-04-09 | 2014-07-11 | Daiichi Sankyo Co Ltd | 吡咯衍生物之阻轉異構物 |
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2009
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- 2009-10-07 EP EP09737501.8A patent/EP2349997B1/en active Active
- 2009-10-07 KR KR1020117010427A patent/KR101643285B1/ko active Active
- 2009-10-07 WO PCT/US2009/059847 patent/WO2010042622A1/en not_active Ceased
- 2009-10-07 CN CN200980139822.5A patent/CN102186817B/zh active Active
- 2009-10-07 JP JP2011531140A patent/JP5767586B2/ja active Active
- 2009-10-07 US US13/122,147 patent/US8487117B2/en active Active
- 2009-10-07 CA CA2736923A patent/CA2736923C/en active Active
- 2009-10-07 ES ES09737501.8T patent/ES2547697T3/es active Active
- 2009-10-07 BR BRPI0920459-8A patent/BRPI0920459B1/pt active IP Right Grant
- 2009-10-08 TW TW098134174A patent/TWI547479B/zh active
- 2009-10-08 TW TW104142529A patent/TWI593674B/zh active
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2011
- 2011-04-06 IL IL212170A patent/IL212170A/en active IP Right Grant
-
2014
- 2014-07-22 JP JP2014148858A patent/JP6121952B2/ja active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006012642A2 (en) * | 2004-07-30 | 2006-02-02 | Exelixis, Inc. | Pyrrole derivatives as pharmaceutical agents |
Non-Patent Citations (2)
| Title |
|---|
| GERHARD BRINGMANN ET AL: "Atroposelective Synthesis of Axially Chiral Biaryl Compounds", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 44, no. 34, 26 August 2005 (2005-08-26), pages 5384-5427 * |
| Stefan E. Boiadjiev ET AL: "Stable Monopyrrole Atropisomers", Monatshefte für Chemie - Chemical Monthly, vol. 133, no. 11, 1 October 2002 (2002-10-01), pages 1469-1480 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP5767586B2 (ja) | 2015-08-19 |
| IL212170A0 (en) | 2011-06-30 |
| US20110263673A1 (en) | 2011-10-27 |
| JP2012505225A (ja) | 2012-03-01 |
| JP6121952B2 (ja) | 2017-04-26 |
| EP2349997B1 (en) | 2015-08-12 |
| KR20110091663A (ko) | 2011-08-12 |
| HK1155163A1 (zh) | 2012-05-11 |
| TWI593674B (zh) | 2017-08-01 |
| US8487117B2 (en) | 2013-07-16 |
| CN102186817A (zh) | 2011-09-14 |
| KR101643285B1 (ko) | 2016-07-29 |
| BRPI0920459B1 (pt) | 2021-12-14 |
| AU2009302371B2 (en) | 2015-02-12 |
| ES2547697T3 (es) | 2015-10-08 |
| TW201627283A (zh) | 2016-08-01 |
| JP2014196365A (ja) | 2014-10-16 |
| AU2009302371A1 (en) | 2010-04-15 |
| IL212170A (en) | 2016-03-31 |
| TW201028377A (en) | 2010-08-01 |
| CN102186817B (zh) | 2017-05-17 |
| CA2736923C (en) | 2016-11-22 |
| CA2736923A1 (en) | 2010-04-15 |
| BRPI0920459A2 (pt) | 2020-08-11 |
| WO2010042622A1 (en) | 2010-04-15 |
| EP2349997A1 (en) | 2011-08-03 |
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