INDOLE DERIVATIVES USEFUL AS ENDOTHELIN RECEPTOR ANTAGONISTS

摘要

Compounds of formula (I), and their pharmaceutically acceptable derivatives, wherein R<1> and R<2> are optional substituents and independently represent C1-6 alkyl, C2-6 alkenyl [optionally substituted by CO2H or CO2(C1-6 alkyl)], C2-6 alkynyl, halogen, C1-3 perfluoroalkyl, (CH2)mAr<1>, (CH2)mHet<1>, (CH2)mCONR<7>R<8>, (CH2)mCO2R<8>, O(CH2)qCO2R<8>, (CH2)mCOR<8>, (CH2)mOR<8>, O(CH2)pOR<8>, (CH2)mNR<7>R<8>, CO2(CH2)qNR<7>R<8>, (CH2)mCN, S(O)nR<8>, SO2NR<7>R<8>, CONH(CH2)mAr<1> or CONH(CH2)mHet<1>; R<3> represents H, C1-6 alkyl, (CH2)pNR<9>R<10>, SO2R<10>, SO2NR<9>R<10>, (CH2)mCOR<10>, C2-6 alkenyl, C2-6 alkynyl, (CH2)mCONR<9>R<10>, (CH2)mCO2R<10>, (CH2)pCN, (CH2)pR<10> or (CH2)pOR<10>; R<4> represents H or C1-6 alkyl; R<5> represents H or OH; R<6> represents phenyl optionally fused to a heterocyclic ring, the group as a whole being optionally substituted; R<7-10> are fully defined herein and may independently represent Ar<2> or Het<2>; Z represents CO2H, CONH(tetrazol-5-yl), CONHSO2O(C1-4 alkyl), CO2Ar<3>, CO2(C1-6 alkyl), tetrazol-5-yl, CONHSO2Ar<3>, CONHSO2(CH2)qAr<3> or CONHSO2(C1-6 alkyl); Ar<1-3> independently represent phenyl, naphthyl, or an aromatic heterocycle, which groups are optionally fused and optionally substituted; and Het<1> and Het<2> independently represent a non-aromatic heterocycle which is optionally substituted; are useful in the treatment of restenosis, renal failure and pulmonary hypertension.