INDOLE DERIVATIVES THROMBOXANE A2 ANTAGONISTS

摘要

Compounds of formula (I) and pharmaceutically acceptable salts and biolabile esters thereof, wherein R<1> is H, C1-C4 alkyl, phenyl optionally substituted by up to three substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, halogen and CF3, or is 1-imidazolyl, 3-pyridyl or 4-pyridyl, R<2> is H or C1-C4 alkyl, R<3> is SO2R<4> or COR<4> where R<4> is C1-C6 alkyl, C1-C3 perfluoroalkyl(CH2)p, C3-C6 cycloalkyl(CH2)p, aryl(CH2)p or heteroaryl(CH2)p, p being 0, 1 or 2, or R<4> may be NR<5>R<6> where R<5> is H or C1-C4 alkyl and R<6> is C1-C6 alkyl, C3-C6 cycloalkyl or aryl, or R<5> and R<6> together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring which may optionally incorporate a carbon-carbon double bond or a further heteroatom linkage selected from O, S, NH, N(C1-C4 alkyl) and N(C1-C5 alkanoyl); X is CH2 or a direct link, with the proviso that when R<1> is 1-imidazolyl then X is CH2; m is 2, or 3; n is 0, 1 or 2 and wherein the group (CH2)nNHR<3> is attached at the 5-position when n is 0 or 1, or at the 5- or 4-position when n is 2. These compounds are selective TXA2 and PGH2 antagonists. Some also inhibit thromboxane synthetase.