ZA200600107B - 2-Substituted phenyl-5,7-dihydrocarbyl-3,7-dihydropyrrolo [2,3-d] pyrimidin-4-one derivatives, the preparation and the pharmaceutical use thereof - Google Patents
2-Substituted phenyl-5,7-dihydrocarbyl-3,7-dihydropyrrolo [2,3-d] pyrimidin-4-one derivatives, the preparation and the pharmaceutical use thereof Download PDFInfo
- Publication number
- ZA200600107B ZA200600107B ZA200600107A ZA200600107A ZA200600107B ZA 200600107 B ZA200600107 B ZA 200600107B ZA 200600107 A ZA200600107 A ZA 200600107A ZA 200600107 A ZA200600107 A ZA 200600107A ZA 200600107 B ZA200600107 B ZA 200600107B
- Authority
- ZA
- South Africa
- Prior art keywords
- dihydropyrrolo
- propyl
- methyl
- ethoxyl
- phenyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title description 35
- 150000001875 compounds Chemical class 0.000 claims description 126
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 97
- 125000000217 alkyl group Chemical group 0.000 claims description 87
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 125000000623 heterocyclic group Chemical group 0.000 claims description 26
- -1 nitro, hydroxyl Chemical group 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 81
- 238000006243 chemical reaction Methods 0.000 description 52
- 239000000543 intermediate Substances 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 23
- BJMZHGBTBCQLNN-UHFFFAOYSA-N 2-propoxybenzoyl chloride Chemical compound CCCOC1=CC=CC=C1C(Cl)=O BJMZHGBTBCQLNN-UHFFFAOYSA-N 0.000 description 22
- 241000700159 Rattus Species 0.000 description 16
- 238000000034 method Methods 0.000 description 16
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 15
- YXHGHIPMRPOBRH-UHFFFAOYSA-N 2-amino-4-methyl-1-propylpyrrole-3-carbonitrile Chemical compound CCCN1C=C(C)C(C#N)=C1N YXHGHIPMRPOBRH-UHFFFAOYSA-N 0.000 description 15
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 125000005936 piperidyl group Chemical group 0.000 description 12
- 125000002757 morpholinyl group Chemical group 0.000 description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 description 11
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 11
- MDKAAWDKKBFSTK-UHFFFAOYSA-N 2-ethoxybenzoyl chloride Chemical compound CCOC1=CC=CC=C1C(Cl)=O MDKAAWDKKBFSTK-UHFFFAOYSA-N 0.000 description 10
- 201000001881 impotence Diseases 0.000 description 10
- 125000001422 pyrrolinyl group Chemical group 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 150000003839 salts Chemical class 0.000 description 9
- HMXQIFUGFZEJEO-UHFFFAOYSA-N 1,2-dihydropyrrol-3-one Chemical group O=C1CNC=C1 HMXQIFUGFZEJEO-UHFFFAOYSA-N 0.000 description 8
- 101150041968 CDC13 gene Proteins 0.000 description 8
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- 230000002401 inhibitory effect Effects 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- QZVGXWVMKIDEID-UHFFFAOYSA-N 2-amino-4-methyl-1h-pyrrole-3-carbonitrile Chemical compound CC1=CNC(N)=C1C#N QZVGXWVMKIDEID-UHFFFAOYSA-N 0.000 description 7
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- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
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- 238000010438 heat treatment Methods 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- FFVFVGBNINLKFY-UHFFFAOYSA-N n-(3-cyano-4-methyl-1h-pyrrol-2-yl)-2-ethoxybenzamide Chemical compound CCOC1=CC=CC=C1C(=O)NC1=C(C#N)C(C)=CN1 FFVFVGBNINLKFY-UHFFFAOYSA-N 0.000 description 7
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
- DEIYFTQMQPDXOT-UHFFFAOYSA-N sildenafil citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 DEIYFTQMQPDXOT-UHFFFAOYSA-N 0.000 description 6
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 5
- 102000015439 Phospholipases Human genes 0.000 description 5
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- 210000003899 penis Anatomy 0.000 description 5
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- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 4
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- 241001465754 Metazoa Species 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB03142399XA CN100374441C (zh) | 2003-06-06 | 2003-06-06 | 二氢吡咯[2，3-d]嘧啶-4-酮衍生物，其制备方法及其制药用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200600107B true ZA200600107B (en) | 2007-04-25 |
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| ZA200600107A ZA200600107B (en) | 2003-06-06 | 2006-01-05 | 2-Substituted phenyl-5,7-dihydrocarbyl-3,7-dihydropyrrolo [2,3-d] pyrimidin-4-one derivatives, the preparation and the pharmaceutical use thereof |
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|---|---|
| US (3) | US7745433B2 (zh) |
| EP (1) | EP1634883B1 (zh) |
| JP (1) | JP4917428B2 (zh) |
| KR (1) | KR101081446B1 (zh) |
| CN (1) | CN100374441C (zh) |
| AP (1) | AP2329A (zh) |
| AT (1) | ATE491710T1 (zh) |
| BR (1) | BRPI0411402A (zh) |
| CA (1) | CA2528008C (zh) |
| DE (1) | DE602004030564D1 (zh) |
| IL (1) | IL172369A (zh) |
| MX (1) | MXPA05013176A (zh) |
| RU (1) | RU2323220C2 (zh) |
| WO (1) | WO2004108726A1 (zh) |
| ZA (1) | ZA200600107B (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100792126B1 (ko) | 2006-04-04 | 2008-01-04 | 동아제약주식회사 | 피라졸로피리미디논 화합물을 유효성분으로 함유하는전립선 비대증 예방 및 치료제 |
| CN101456862B (zh) * | 2007-12-12 | 2012-10-24 | 上海特化医药科技有限公司 | 含有吡唑并嘧啶酮的苯基胍衍生物、其药物组合物及其制备方法和用途 |
| CN101747282A (zh) | 2008-12-10 | 2010-06-23 | 上海特化医药科技有限公司 | 一类含有嘧啶酮苯基的化合物、其药物组合物及其制备方法和用途 |
| AR077898A1 (es) | 2009-08-26 | 2011-09-28 | Nycomed Gmbh | Metilpirrolopirimidincarboxamidas |
| CN102311447B (zh) * | 2010-07-07 | 2013-11-27 | 中国科学院广州生物医药与健康研究院 | 杂环并嘧啶酮类dpp-iv抑制剂 |
| CN102329325B (zh) * | 2010-07-07 | 2013-11-27 | 中国科学院广州生物医药与健康研究院 | 吡咯并嘧啶酮类dpp-iv抑制剂 |
| KR101969526B1 (ko) * | 2011-02-28 | 2019-04-17 | 고쿠리츠켄큐카이하츠호진 고쿠리츠쥰칸키뵤 겐큐센터 | 악성 종양 전이 억제용 의약 |
| BR112014030416A2 (pt) * | 2012-06-07 | 2017-06-27 | Hoffmann La Roche | composto, métodos para a inibição da tankyrase 1 e para o tratamento do câncer, utilização de um composto, composição e invenção. |
| CN104530054B (zh) * | 2014-12-19 | 2018-01-19 | 扬子江药业集团有限公司 | 盐酸优克那非的多晶型物及其制备方法 |
| CN114042071A (zh) * | 2015-07-08 | 2022-02-15 | 珠海津之敦医药科技有限公司 | 尤克那非新用途 |
| RU2758373C2 (ru) * | 2017-05-22 | 2021-10-28 | Топадур Фарма Аг | Новые активаторы растворимой гуанилатциклазы и ингибиторы фосфодиэстеразы с двойным механизмом действия и их применение |
| CN112266349B (zh) * | 2020-11-17 | 2022-02-15 | 上海凌凯医药科技有限公司 | 一种制备2-氨基-4-甲基-1-丙基-1h-吡咯-3-甲腈的方法 |
| CN112961160A (zh) * | 2021-03-05 | 2021-06-15 | 遂成药业股份有限公司 | 一种西地那非的改良合成工艺 |
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| US5235053A (en) * | 1992-06-22 | 1993-08-10 | Eli Lilly And Company | Process for the synthesis of 4-hydroxy-5-halopyrrold[2,3-d]pyrimidine intermediates |
| GB9301192D0 (en) | 1993-06-09 | 1993-06-09 | Trott Francis W | Flower shaped mechanised table |
| GB9423911D0 (en) | 1994-11-26 | 1995-01-11 | Pfizer Ltd | Therapeutic agents |
| GB9612514D0 (en) | 1996-06-14 | 1996-08-14 | Pfizer Ltd | Novel process |
| US5958926A (en) * | 1996-11-01 | 1999-09-28 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
| JP4166859B2 (ja) * | 1997-03-17 | 2008-10-15 | 富士フイルム株式会社 | ２−アミノピロール誘導体及びその製造方法 |
| GB9708831D0 (en) | 1997-04-30 | 1997-06-25 | Unilever Plc | Suspensions with high storage stability, comprising an aqueous silicate solution and filler material |
| DK1049695T3 (da) | 1997-11-12 | 2002-05-13 | Bayer Ag | 2-Phenyl-substituerede imidazotriazinoner som phosphodiesterase-inhibitorer |
| DE29806778U1 (de) | 1998-04-15 | 1999-09-02 | Grote & Hartmann | Schraubanschluß |
| SK15532000A3 (sk) | 1998-04-20 | 2001-12-03 | Pfizer Inc. | Pyrazolopyrimidínové inhibítory cgmp pde5 na použitie na liečbu sexuálnych dysfunkcií, spôsob ich prípravy, medziprodukty a farmaceutický prostriedok s ich obsahom |
| US6878716B1 (en) * | 1998-06-02 | 2005-04-12 | Osi Pharmaceuticals, Inc. | Compounds specific to adenosine A1 receptor and uses thereof |
| GB9823103D0 (en) * | 1998-10-23 | 1998-12-16 | Pfizer Ltd | Pharmaceutically active compounds |
| ATE250063T1 (de) | 1998-10-23 | 2003-10-15 | Pfizer | Pyrazolopyrimidinone, cgmp pde5 inhibitoren, zur behandlung von sexuellen funktionsstörungen |
| KR100353014B1 (ko) | 1998-11-11 | 2002-09-18 | 동아제약 주식회사 | 발기부전 치료에 효과를 갖는 피라졸로피리미디논 화합물 |
| IN186584B (zh) | 1999-03-26 | 2001-10-06 | Kopran Ltd | |
| GB9909135D0 (en) * | 1999-04-22 | 1999-06-16 | Univ Wales Medicine | Cystic fibrosis medicaments |
| GB9924020D0 (en) | 1999-10-11 | 1999-12-15 | Pfizer Ltd | Pharmaceutically active compounds |
| KR100358083B1 (ko) * | 2000-02-17 | 2002-10-25 | 에스케이케미칼주식회사 | 피롤로피리미디논 유도체와 이의 제조방법, 그리고 이의용도 |
| KR100377782B1 (ko) | 2000-06-23 | 2003-03-29 | 동아제약 주식회사 | 발기부전 치료에 효과를 갖는 피라졸로피리미디논화합물의 제조방법 |
| US6849735B1 (en) * | 2000-06-23 | 2005-02-01 | Merck Eprova Ag | Methods of synthesis for 9-substituted hypoxanthine derivatives |
| WO2002016364A1 (en) | 2000-08-23 | 2002-02-28 | Lg Life Sciences Ltd. | Polyethoxylated pyrazolo pyrimidinone derivatives, process for preparation thereof and pharmaceutical compositions comprising the same for the treatment of impotence |
| GB0106661D0 (en) * | 2001-03-16 | 2001-05-09 | Pfizer Ltd | Pharmaceutically active compounds |
| DE10163991A1 (de) * | 2001-12-24 | 2003-07-03 | Merck Patent Gmbh | Pyrrolo-pyrimidine |
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2004
- 2004-05-14 AP AP2006003481A patent/AP2329A/xx active
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- 2004-05-14 DE DE602004030564T patent/DE602004030564D1/de active Active
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- 2004-05-14 WO PCT/CN2004/000487 patent/WO2004108726A1/zh active Application Filing
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| Publication number | Publication date |
|---|---|
| WO2004108726A1 (fr) | 2004-12-16 |
| JP2008500944A (ja) | 2008-01-17 |
| KR20060036396A (ko) | 2006-04-28 |
| US20100204223A1 (en) | 2010-08-12 |
| EP1634883A4 (en) | 2008-07-02 |
| EP1634883A1 (en) | 2006-03-15 |
| EP1634883B1 (en) | 2010-12-15 |
| JP4917428B2 (ja) | 2012-04-18 |
| DE602004030564D1 (de) | 2011-01-27 |
| MXPA05013176A (es) | 2006-06-23 |
| US20060173025A1 (en) | 2006-08-03 |
| US20080167462A1 (en) | 2008-07-10 |
| CN100374441C (zh) | 2008-03-12 |
| US7741483B2 (en) | 2010-06-22 |
| AP2329A (en) | 2011-12-02 |
| CA2528008A1 (en) | 2004-12-16 |
| RU2005141447A (ru) | 2007-07-20 |
| CN1552714A (zh) | 2004-12-08 |
| IL172369A0 (en) | 2006-04-10 |
| BRPI0411402A (pt) | 2006-10-31 |
| KR101081446B1 (ko) | 2011-11-08 |
| ATE491710T1 (de) | 2011-01-15 |
| IL172369A (en) | 2014-01-30 |
| AP2006003481A0 (en) | 2006-02-28 |
| RU2323220C2 (ru) | 2008-04-27 |
| US8461165B2 (en) | 2013-06-11 |
| US7745433B2 (en) | 2010-06-29 |
| CA2528008C (en) | 2010-02-16 |
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