INDOLE DERIVATIVES USEFUL AS ENDOTHELIN RECEPTOR ANTAGONISTS

摘要

Compounds of formula (I), and their pharmaceutically acceptable derivatives, wherein R?1 and R2¿ are optional substituents and independently represent C¿1-6? alkyl, C2-6 alkenyl [optionally substituted by CO2H or CO2(C1-6 alkyl)], C2-6 alkynyl, halogen, C1-3 perfluoroalkyl, (CH2)mAr?1, (CH¿2)mHet1, (CH2)mCONR?7R8, (CH¿2)mCO2R8, O(CH¿2?)qCO2R?8, (CH¿2)mCOR8, (CH2)mOR8, O(CH¿2?)pOR?8, (CH¿2)mNR7R8, CO2(CH2)qNR?7R8, (CH¿2)mCN, S(O)nR8, SO2NR7R8, CONH(CH¿2)mAr?1 or CONH(CH¿2?)mHet?1; R3¿ represents H, C¿1-6? alkyl, (CH2)pNR?9R10, SO¿2R10, SO2NR?9R10, (CH¿2)mCOR10, C2-6 alkenyl, C2-6 alkynyl, (CH2)mCONR?9R10, (CH¿2)mCO2R10, (CH2)pCN, (CH2)pR10 or (CH¿2?)pOR?10; R4¿ represents H or C¿1-6? alkyl; R?5¿ represents H or OH; R6 represents phenyl optionally fused to a heterocyclic ring, the group as a whole being optionally substituted; R7-10 are fully defined herein and may independently represent Ar?2 or Het2¿; Z represents CO¿2?H, CONH(tetrazol-5-yl), CONHSO2O(C1-4 alkyl), CO2Ar?3, CO¿2(C1-6 alkyl), tetrazol-5-yl, CONHSO2Ar3, CONHSO¿2?(CH2)qAr?3¿ or CONHSO¿2?(C1-6 alkyl); Ar?1-3¿ independently represent phenyl, naphthyl, or an aromatic heterocycle, which groups are optionally fused and optionally substituted; and Het1 and Het2 independently represent a non-aromatic heterocycle which is optionally substituted; are useful in the treatment of restenosis, renal failure and pulmonary hypertension.