发明授权
US09162979B2 1,5-Diary1-2-alkylpyrrole-3-substituted nitro esters, selective COX-2 inhibitors and nitric oxide donors
有权
1,5-二辛基-2-烷基吡咯-3-取代的硝基酯,选择性COX-2抑制剂和一氧化氮供体
- 专利标题: 1,5-Diary1-2-alkylpyrrole-3-substituted nitro esters, selective COX-2 inhibitors and nitric oxide donors
- 专利标题(中): 1,5-二辛基-2-烷基吡咯-3-取代的硝基酯,选择性COX-2抑制剂和一氧化氮供体
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申请号: US13820533申请日: 2011-09-07
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公开(公告)号: US09162979B2公开(公告)日: 2015-10-20
- 发明人: Antonio Giordani , Mariangela Biava , Maurizio Anzini , Vincenzo Calderone , Lucio Claudio Rovati
- 申请人: Antonio Giordani , Mariangela Biava , Maurizio Anzini , Vincenzo Calderone , Lucio Claudio Rovati
- 申请人地址: IT Monza
- 专利权人: ROTTAPHARM BIOTECH S.R.L.
- 当前专利权人: ROTTAPHARM BIOTECH S.R.L.
- 当前专利权人地址: IT Monza
- 代理商 Robert E. Alderson, Jr.
- 优先权: ITTO2010A0739 20100907
- 国际申请: PCT/IB2011/053914 WO 20110907
- 国际公布: WO2012/032479 WO 20120315
- 主分类号: A61K31/40
- IPC分类号: A61K31/40 ; A01N43/36 ; C07D207/337 ; A61K45/00 ; C07D207/333 ; C07D207/335
摘要:
1,5-diaryl-2-alkylpyrrole-3-substituted nitro esters, of Formula (I) are provided. Such compounds are potent and selective COX-2 inhibitors which are able to release NO in concentrations that make it possible to counteract the side effects due to selective COX-2 inhibition, without giving rise to hypotensive effects. Formula (I) includes compounds wherein the groups R′ and R″ are: —H, —F, —Cl, —Br, —CH3, —CF3, —OCH3, —SCH3, R1 is methyl, ethyl, trifluoromethyl, hydroxymethyl, methoxymethyl and the substituent in position −3 of the pyrrole ring is a chain, where the groups X, Y, Z, W and R2 are: X is a carbonyl or a group —(CHR3)—, Y is an oxygen atom or the group —NR3— and Z is a carbonyl or a group —(CHR3)—, or a [—CH(COOH)—] group, or a group —(NR3)—, W is an aliphatic chain substituted with one or two (—O—NO2) groups, R2 is: —H, —OH, —OCH3, or —NHR3. R3 is: —H, —CH3, —CH2CH3, [—CH2(CH3)2]. R′″ is methylsulphonyl or sulphonamido. Pharmaceutical formulations and methods of making an using such formulations are also provided.
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