9-DEOXY-9A-METHYLENE ISOSTERES OF PGI.SUB.2 AND PROCESS FOR THEIR PREPARATION

摘要

The invention relates to new compounds of formula I < IMG > I wherein R is (a) a free or esterified carboxy group; (b) -C(OR')3, where each R' group is independently C1-C6-alkyl or phenyl; (c) -CH2-R", where R" is hydroxy or C2-C7-alkoxy; (d) < IMG >, where Ra and Rb are chosen independently from the group hydrogen, C1-C6-alkyl, C2-C6-alkanoyl and phenyl; (e) -C?N; (f) < IMG > radical; (g) -CHO; or (h) < IMG > radical where each X' is independently -O- or -S- and the R'a and R'b groups, whether the same or different, are C1-C6-alkyl or together form a straight or branched C2-C6-alkenylene chain; D is: < IMG > (trans), -C?C-, < IMG >, -O-, -S-, or < IMG >, where Rc may be hydrogen, C1-C6-alkyl or C2-C6-alkanoyl; one of R1 and R2 and, independently, one of R3 and R4 is hydrogen, C1-C6-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, phenyl, or aryl-C1-C6-alkyl and the other is hydrogen, hydroxy, C1-C6-alkoxy or arylC1-C6-alkoxy, or, R1 and R2 and, independently, R3 and R4 together form an oxo group; each R5 and R6, whether the same or different, may be hydrogen, C1-C6-alkyl or halogen, or R5, R6 and the carbon atom to which they are bound form a < IMG > or < IMG > radical; Y is: -C?C-, < IMG > (trans), < IMG > (cis) where z is halogen, -NH-CO- or -NH-CH2-; X is: -(CH2)m3-in which m3 is zero or 1, < IMG > (cis), < IMG > (trans), -O-, -S-, or < IMG > where Rc is as defined above; m1, m2, n1 and n2, whether the same or different, may be zero or an integer between 0 and 12 such that each sum m1 + m2 and n1 + n2 is less than or equal to 15; p and q are independently zero or an integer between 1 and 3 such that the sum p + q is an integer of 1 to 6; R7 is (a') hydrogen; (b') Cl-C4-alkyl; or (c') an aryl group, either unsubstituted or substituted with one or more of the following: halogen, halo-Cl-C6-alkyl, Cl-C6-alkyl, Cl-C6-alkoxy, phenyl; and the lactones derived from compounds of formula I and the pharmaceutically or veterinarily acceptable salts thereof. The compounds display bronchodilator, luteolytic, anti-ulcerogenic and platelet anti-aggregant activity.