发明名称 |
4-CARBONYL SUBSTITUTED 1,1,2-TRIMETHYL-1A,4,5,5A-TETRAHYDRO-1H-4-AZA-CYCLOPROPA'A!PENTALENE DERIVATIVES AS AGONISTS FOR THE G-PROTEIN-COUPLED RECEPTOR S1P1/EDG1 AND IMMUNOSUPPRESSIVE AGENTS |
摘要 |
<p>The invention relates to novel pyrrole compounds of the formula (I) wherein A represents -CH2CH2-, -CH=CH-, or -NH-CH2; Ar represents phenyl; mono-, di-, or tri-substituted phenyl, wherein the substituents are independently selected from halogen, lower alkyl, lower alkoxy, hydroxy-lower alkyl, hydroxy-lower alkoxy, 1-glyceryl, 2-glyceryl, cycloalkyl, mono- or di-lower alkylamino, methylenedioxy, ethylenedioxy, trifluoromethyl and trifluoromethoxy; or unsubstituted mono- or di-substituted 2-, 3- or 4-pyridyl, wherein the substituents are independently selected from lower alkoxy and hydroxy-lower alkoxy. The present invention provides novel compounds of formulae (I), (II) and (III) that are agonists for the G protein-coupled receptor S1P1/EDG1 and have a powerful and long-lasting immunosuppressive effect which is achieved by reducing the number of cirulating and infiltrating T- and B-lymphocytes, whitout affecting their maturation, memory or expansion. The reduction of circulating T-/B-lymphocytes as a result of S1P1/EDG1 agonism, possibly in combination with the observed improvement of endothelial cell layer function associated with S1P1/EDG1 activation, makes such compounds useful to treat uncontrolled inflammatory disease and to improve vascular functionality.</p> |
申请公布号 |
WO2005123677(A1) |
申请公布日期 |
2005.12.29 |
申请号 |
WO2005EP06348 |
申请日期 |
2005.06.14 |
申请人 |
ACTELION PHARMACEUTICALS LTD;BOLLI, MARTIN;BUR, DANIEL;CLOZEL, MARTINE;FISCHLI, WALTER;LEHMANN, DAVID;MATHYS, BORIS;MUELLER, CLAUS;NAYLER, OLIVIER;SCHERZ, MICHAEL;WELLER, THOMAS |
发明人 |
BOLLI, MARTIN;BUR, DANIEL;CLOZEL, MARTINE;FISCHLI, WALTER;LEHMANN, DAVID;MATHYS, BORIS;MUELLER, CLAUS;NAYLER, OLIVIER;SCHERZ, MICHAEL;WELLER, THOMAS |
分类号 |
A61K31/403;A61P37/06;C07D209/94;(IPC1-7):C07D209/94 |
主分类号 |
A61K31/403 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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