9,11-Methano-13-aza-11a-carbathrombanoic acid analogues

摘要

The 9,11-methano-13-aza-11a-carbathrombanoic acid analogues of the general formula: V [wherein A represents CH2CH2(CH2)m, (i) (ii) CH2O(CH2)mor (iii) (iv) (in which m is an integer of 1 to 6, the double bond between the carbon atoms in positions 5 and 6 in (iv) is in cis or trans-configuration or a mixture thereof and the phenylene group in (iv) represents o-, m- or p-phenylene), R1 represents a hydrogen atom or a straight- or branched-chain alkyl group of 1 to 12 carbon atoms, two R2 both represent hydrogen atoms or methyl groups, R3 represents a hydrogen atom or a hydroxy group, R4 represents a single bond or a straight- or branched-chain alkylene group of 1 to 5 carbon atoms, R5 represents (i) a straight- or branched-chain alkyl, alkoxy or alkylthio group of 1 to 8 carbon atoms, (ii) a cycloalkyl or cycloalkyloxy group of 4 to 7 carbon atoms being unsubstituted or substituted by at least one straight- or branched-chain alkyl group of 1 to 8 carbon atoms or in which Z represents a single bond, an oxygen atom or a sulfur atom and R6 may occupy any of the free positions on the phenyl ring and represents a hydrogen atom, a halogen atom, a hydroxy group, a straight- or branched-chain alkyl or alkoxy group of 1 to 5 carbon atoms, a trihalomethyl group, an amino group or a mono- or dialkyl-amino group of 1 to 5 carbon atoms) and the wavy line attached to the carbon atom in position 15 represents alpha - or beta -configuration or a mixture thereof, provided that, when R3 represents a hydroxy group and R4 represents a single bond, R5 does not represent an alkoxy group, an alkylthio group, a cycloalkyloxy group, a phenoxy group and a phenylthio group], and cyclodextrin clathrates thereof, and when R1 represents a hydrogen atom, non-toxic salts thereof, possess strong inhibitory activities on platelet aggregation and on aorta contraction, and are useful for prevention and treatment of diseases which are induced by thromboxane A2.