6,9-Oxido prostaglandin analogues - useful as antihypertensives, vasodilators, thrombocyte aggregation inhibitors, etc.

摘要

Prostaglandin analogues of formula (I) and their salts are new. In (I) R is opt. esterified COOH, C(OR')3, CH2OH, CONRaRb, 1H-tetrazol-5-yl or CN; where each R' is 1-6C alkyl or phenyl; Ra and Rb are H, 1-6C alkyl, 2-6C alkanoyl or phenyl; Z1 is H or halogen; p is 0-7; q is 1 or 2; R1 is H, OH, 1-6C alkoxy, aralkoxy or acyloxy; Y is CH2CH2, C=C, cis-CH=CZ2 or trans-CH=CZ2; where Z2 is H or halogen. One of R2 and R5 is H, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl or aryl, and the other is OH, 1-6C alkoxy or aralkoxy, or R2 and R5 together form O; R3 and R4 are H, 1-6C alkyl or F, or CR3R4 is vinylidene or cyclopropylidene; n and n' are 0-6; X is O, S or (CH2)m (where m is 0 or 1). R6 is H, 1-4C alkyl or a 3-9C cycloaliphatic gp. opt. mono-or poly-substd. by 1-6C alkyl and/or alkoxy. (I) can be used for the same therapeutic purposes as natural prostaglandins, but generally have better chemical stability and resistance to 15-PG-dehydrogenase enzymes. They are useful as antihypertensives and vasodilators (more active than PGE1 and PGE2); thrombocyte aggrega-inhibitors; oxytocic agents (more selective than PGF2 alpha); luteolytic agents; gastric secretion inhibitors and antiulcer agents (more effective than PGE3); and bronchodilators. A typical cpd. is 13-trans-6 beta H-6,9 alpha-oxido-155S-hydroxy-13-prostenoic acid.