19-Hydroxy-19-methyl-6,9α-epoxymethano-PGF compounds

Claim 1

A prostacyclin-type compound of the formula ##STR3## wherein A 2 is --CH 2 O-- with --CH 2 bonded to the cyclopentane ring and E 1 is --CH 2 --; wherein L 1 is (1) --(CH 2 ) n --, wherein n is one to 5, inclusive, (2) --(CH 2 ) p --CF 2 --, wherein p is 2, 3, or 4; or (3) --CH 2 --CH═CH--; wherein M 1 is ##STR4## wherein Q is oxo, α--H:β--H, α--OH:β--R 4 , or α--R 4 :β--OH, wherein R 4 is hydrogen or alkyl of one to 4 carbon atoms, inclusive; wherein R 1 is (1) --COOR 3 , (2) --CH 2 OH, (3) --CH 2 N(R 7 )(R 8 ), (4) --CO--N(R 7 )(R 8 ), (5) --CO--NH--SO 2 --R 15 , or (6) tetrazolyl, wherein R 3 is (a) hydrogen, (b) alkyl of one to 12 carbon atoms, inclusive, (c) cycloalkyl of 3 to 10 carbon atoms, inclusive, (d) aralkyl of 7 to 12 carbon atoms, inclusive, (e) phenyl, (f) phenyl substituted with one, 2, or 3 chloro or alkyl groups of one to 3 carbon atoms, inclusive; (g) --(Ph)--CO--CH 3 , (h) --(p-Ph)--NH--CO--(p-Ph)--NH--CO--CH 3 , (i) --(p-Ph)--NH--CO--(p-Ph), (j) --(p-Ph)--NH--CO--CH 3 , (k) --(p-Ph)--NH--CO--NH 2 , (l) --(p-Ph)--CH═N--NH--CO--NH 2 , (m) β--naphthyl, (n) --CH 2 --CO--R 16 , wherein --(Ph)-- is inter-phenylene and --(p-Ph) is inter-para-phenylene or para-phenyl; wherein R 16 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, or (o) a pharmacologically acceptable cation; wherein R 7 and R 8 are hydrogen, alkyl of one to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different, and wherein R 15 is hydrogen, alkyl of one to 12 carbon atoms, inclusive, phenyl, phenyl-substituted with one, 2, or 3 chloro or alkyl groups of one to 3 carbon atoms, inclusive, or phenyl substituted with hydroxycarbonyl or alkoxycarbonyl of one to 4 carbon atoms, inclusive, in the alkoxy group wherein R 2 is hydrogen, hydroxyl, or hydroxymethyl, wherein R 5 and R 6 are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R 5 and R 6 is fluoro only when the other is hydrogen or fluoro, and wherein X is (1) trans--CH═CH--, (2) cis--CH═CH--, (3) --C.tbd.C--, or (4 ) --CH 2 CH 2 --.