Esters of 1-hydroxy prostaglandins - with stronger, more selective and longer lasting activities

摘要

Prostane derivs. of formula (I), esp. those of formula (II) are new: (P is any substd. prostane residue; R1 = residue of a 1-15C organic carboxylic or sulphonic acid, of an inorg. acid or the gp. CUNHR6; U = O or S; R6 = opt. substd. acid, aryl, cycloalkyl or alkyl gp.; R2 and R3 = H or 1-4C alkyl; A is CH2CH2 or cis or trans CH=CH; B is CH2CH2, trans CH=CH, C C or - H CH- with the CH2 in a or beta-posn., W = CHOH, CO (both opt. functionally modified) or - (CH3)-, the OH being in alpha or beta posn. and opt. functionally modified; D = opt. branched 1-5C alkylene or C C; E = O, S or direct bond; D and E can together represent a direct bond; R4 = alkyl, cycloalkyl, opt. substd. aryl, benzodioxol-2-yl or heterocyclyl; Z = CO or opt. modified CHOH; X Y = - H CH-, CH2CH(...R5) or CH2CO when Z = CHOH or is CH2CH(...R5) or CH=CH when Z = CO; R5 = alkyl or opt. modified OH). Also new are intermediates (III) when R2 and R3 are not both H; (I) are similar to natural PG's but their action is stronger, more selective and longer lasting. They are variously useful as luteolytics; for termination of pregnancy (some 100 times as active as PGF2a); to synchronise ovulation in cows etc.; as bronchodilators, gastric acid secretion inhibitors; anti-arrhythmics; antihypertensives and diuretics. They effect uterine muscle with virtually no effect on intestinal or vascular muscles.