申请人:Pfizer Inc.
公开号:US06017945A1
公开(公告)日:2000-01-25
Compounds of formula (I), and their pharmaceutically acceptable derivatives, wherein R.sup.1 and R.sup.2 are optional substituents and independently represent C.sub.1-6 alkyl, C.sub.2-6 alkenyl [optionally substituted by CO.sub.2 H or CO.sub.2 (C.sub.1-6 alkyl)], C.sub.2-6 alkynyl, halogen, C.sub.1-3 perfluoroalkyl, (CH.sub.2).sub.m Ar.sup.1, (CH.sub.2).sub.m Het.sup.1, (CH.sub.2).sub.m CONR.sup.7 R.sup.8, (CH.sub.2).sub.m CO.sub.2 R.sup.8, O(CH.sub.2).sub.q CO.sub.2 R.sup.8, (CH.sub.2).sub.m COR.sup.8, (CH.sub.2).sub.m OR.sup.8, O(CH.sub.2).sub.p OR.sup.8, (CH.sub.2).sub.m NR.sup.7 R.sup.8, CO.sub.2 (CH.sub.2).sub.q NR.sup.7 R.sup.8, (CH.sub.2).sub.m CN, S(O).sub.n R.sup.8, SO.sub.2 NR.sup.7 R.sup.8, CONH(CH.sub.2).sub.m Ar.sup.1 or CONH(CH.sub.2).sub.m Het.sup.1 ; R.sup.3 represents H, C.sub.1-6, alkyl, (CH.sub.2).sub.p NR.sup.9 R.sup.10, SO.sub.2 R.sup.10, SO.sub.2 NR.sup.9 R.sup.10, (CH.sub.2).sub.m COR.sup.10, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.m CONR.sup.9 R.sup.10, (CH.sub.2).sub.m CO.sub.2 R.sup.10, (CH.sub.2).sub.p CN, (CH.sub.2).sub.p R.sup.10 or (CH.sub.2).sub.p OR.sup.10 ; R.sup.4 represents H or C.sub.1-6 alkyl; R.sup.5 represents H or OH; R.sup.6 represents phenyl optionally fused to a heterocyclic ring, the group as a whole being optionally substituted; R.sup.7-10 are fully defined herein and may independently represent Ar.sup.2 or Het.sup.2 ; Z represents CO.sub.2 H, CONH(tetrazol-5-yl), CONHSO.sub.2 O(C.sub.1-4 alkyl), CO.sub.2 Ar.sup.3, CO.sub.2 (C.sub.1-6 alkyl), tetrazol-5-yl, CONHSO.sub.2 Ar.sup.3, CONHSO.sub.2 (CH.sub.2).sub.q Ar.sup.3 or CONHSO.sub.2 (C.sub.1-6 alkyl); Ar.sup.1-3 independently represent phenyl, naphthyl, or an aromatic heterocycle, which groups are optionally fused and optionally substituted; and Het.sup.1 and Het.sup.2 independently represent a non-aromatic heterocycle which is optionally substituted; are useful in the treatment of restenosis, renal failure and pulmonary hypertension.
式(I)的化合物及其药用可接受的衍生物,其中R.sup.1和R.sup.2是可选取代基团,独立表示C.sub.1-6烷基,C.sub.2-6烯基[可选择性地被CO.sub.2 H或CO.sub.2(C.sub.1-6烷基)取代],C.sub.2-6炔基,卤素,C.sub.1-3全氟烷基,(CH.sub.2).sub.m Ar.sup.1,(CH.sub.2).sub.m Het.sup.1,(CH.sub.2).sub.m CONR.sup.7 R.sup.8,(CH.sub.2).sub.m CO.sub.2 R.sup.8,O(CH.sub.2).sub.q CO.sub.2 R.sup.8,(CH.sub.2).sub.m COR.sup.8,(CH.sub.2).sub.m OR.sup.8,O(CH.sub.2).sub.p OR.sup.8,(CH.sub.2).sub.m NR.sup.7 R.sup.8,CO.sub.2(CH.sub.2).sub.q NR.sup.7 R.sup.8,(CH.sub.2).sub.m CN,S(O).sub.n R.sup.8,SO.sub.2 NR.sup.7 R.sup.8,CONH(CH.sub.2).sub.m Ar.sup.1或CONH(CH.sub.2).sub.m Het.sup.1;R.sup.3表示H,C.sub.1-6烷基,(CH.sub.2).sub.p NR.sup.9 R.sup.10,SO.sub.2 R.sup.10,SO.sub.2 NR.sup.9 R.sup.10,(CH.sub.2).sub.m COR.sup.10,C.sub.2-6烯基,C.sub.2-6炔基,(CH.sub.2).sub.m CONR.sup.9 R.sup.10,(CH.sub.2).sub.m CO.sub.2 R.sup.10,(CH.sub.2).sub.p CN,(CH.sub.2).sub.p R.sup.10或(CH.sub.2).sub.p OR.sup.10;R.sup.4表示H或C.sub.1-6烷基;R.sup.5表示H或OH;R.sup.6表示苯基,可选地融合到杂环环,整体可选取代;R.sup.7-10在此完全定义,可独立表示Ar.sup.2或Het.sup.2;Z表示CO.sub.2 H,CONH(tetrazol-5-yl),CONHSO.sub.2O(C.sub.1-4烷基),CO.sub.2 Ar.sup.3,CO.sub.2(C.sub.1-6烷基),tetrazol-5-yl,CONHSO.sub.2 Ar.sup.3,CONHSO.sub.2(CH.sub.2).sub.q Ar.sup.3或CONHSO.sub.2(C.sub.1-6烷基);Ar.sup.1-3独立表示苯基,萘基或芳香杂环,这些基团可选地融合和可选取代;Het.sup.1和Het.sup.2独立表示可选取代的非芳香杂环;在治疗再狭窄、肾功能衰竭和肺动脉高压方面是有用的。