Benzopyran compounds, derivatives of prostaglandins

Claim 1

A compound of the formula wherein R is --CH 2 -- or --O--; wherein Z is --CH 2 --; --CH 2 CH 2 --; --CF 2 --; --CF 2 CH 2 ; or wherein --Z--R-- taken together is trans--CH═CH--CH 2 -- or trans--CH═CH--; wherein Q is (1) --COOR 5 , wherein R 5 is (a) hydrogen, (b) (C 1 -C 12 )alkyl, (c) (C 3 -C 10 )cycloalkyl, (d) (C 7 -C 12 )aralkyl, (e) phenyl optionally substituted with one, 2 or 3 chloro or (C 1 -C 4 )alkyl, (f) phenyl substituted in the para-position with --NHCOR 6 , --COR 7 , --OC(O)R 8 or --CH═N--NHCONH 2 , wherein R 6 is methyl, phenyl, acetamidophenyl, ,enzamidophenyl or --NH 2 ; R 7 is methyl, phenyl, --NH 2 , or methoxy; and R 8 is phenyl or acetamidophenyl; (g) phthalidyl, (h) 3-(5,5-dimethyl-1,3,2-dioxaphosphorinan-2-yl)-2-oxopropan-1-yl P-oxide, (i) 3-(5,5-di(hydroxymethyl)-1,3,2-dioxaphosphorinan-2-yl)-2-oxopropan-1-yl P-oxide, or (j) a pharmacologically acceptable cation; (2) --CH 2 OH; (3) --COL 2 , wherein L 2 is (a) an amino group of the formula --NR 9 R 10 wherein R 9 is hydrogen or (C 1 -C 12 )alkyl and R 10 is (i) hydrogen (ii) (C 1 -C 12 )alkyl (iii) (C 3 -C 10 )cycloalkyl, (iv) (C 7 -C 12 )aralkyl (v) phenyl optionally substituted with one, 2 or 3 chloro, (C 1 -C 3 )alkyl, hydroxy, carboxy, (C 2 -C 5 )alkoxycarbonyl, or nitro, (vi) (C 2 -C 5 )carboxyalkyl, (vii) (C 2 -C 5 )carbamoylalkyl, (viii) (C 2 -C 5 )cyanoalkyl, (ix) (C 3 -C 6 )acetylalkyl, (x) (C 7 -C 12 )benzoylalkyl, optionally substituted by one, 2, or 3 chloro, (C 1 -C 3 )alkyl, hydroxy, (C 1 -C 3 )alkoxy, carboxy, (C 2 -C 5 )-alkoxycarbonyl, or nitro, (xi) pyridyl, optionally substituted by one, 2, or 3 chloro, (C 1 -C 3 )alkyl, or (C 1 -C 3 )alkoxy, (xii) (C 6 -C 9 )pyridylalkyl optionally substituted by one, 2, or 3 chloro, (C 1 -C 3 )alkyl, hydroxy, or (C 1 -C 3 )alkyl, (xiii) (C 1 -C 4 )hydroxyalkyl, (xiv) (C 1 -C 4 )dihydroxyalkyl, (xv) (C 1 -C 4 )trihydroxyalkyl; (b) cycloamine selected from the group consisting of pyrolidino, piperidino, morpholino, piperazino, hexamethyleneimino, pyrroline, or 3,4-didehydropiperidinyl optionally substituted by one or 2 (C 1 -C 12 )alkyl; (c) carbonylamino of the formula --NH 11 COR 10 , wherein R 11 is hydrogen or (C 1 -C 4 )alkyl and R 10 is other than hydrogen, but otherwise defined as above; (d) sulfonylamino of the formula --NR 11 SO 2 R 10 , wherein R 11 and R 10 are defined in (c); (4) --CH 2 NL 3 L 4 , wherein L 3 and L 4 are hydrogen or (C 1 -C 4 )alkyl, being the same or different, or the pharmacologically acceptable acid addition salts thereof when Q is --CH 2 NL 3 L 4 ; (5) --CN; ##STR23## wherein R 1 is oxo; H,H; α-OR 12 ,β-H; α-H,β-OR 12 ; α-CH 2 OR 12 ,β-H; α-H,β-CH 2 OR 12 wherein R 12 is hydrogen or a hydroxyl protective group; wherein Y is trans --CH═CH--, cis--CH═CH--, --CH 2 CH 2 --, or --C.tbd.C--; wherein M is α-OR 12 ,β-R 14 ; or α-R 14 ,β-OR 12 , wherein R 12 is as defined above, and R 14 is hydrogen or methyl; wherein L 1 is α-R 15 ,β-R 16 ; α-R 16 ,β-R 15 ; or a mixture thereof wherein R 15 and R 16 are hydrogen, methyl, or fluoro being the same or different with the proviso that one of R 15 and R 16 is fluoro only when the other of R 15 and R 16 is hydrogen or fluoro; wherein R 17 is (1) --C m H 2 .sbsb.m CH 3 wherein m is an integer of from one to 5, (2) phenoxy optionally substituted by one, 2, or 3 chloro, fluoro, trifluoromethyl, (C 1 -C 3 )alkyl, or (C 1 -C 3 )alkoxy, with the proviso that not more than two substituents are other than alkyl and with the proviso that R 17 is phenoxy or substituted phenoxy, only when R 15 and R 16 are hydrogen or methyl, being the same or different; (3) phenyl, benzyl, phenylethyl, or phenylpropyl optionally substituted on the aromatic ring by one, 2, or 3 chloro, fluoro, trifluoromethyl (C 1 -C 3 )alkyl, or (C 1 -C 3 )alkoxy, with the proviso that not more than two substituents are other than alkyl, (4) cis--CH═CH--CH 2 CH 3 , (5) --(CH 2 ) 2 --CH(OH)--CH 3 , (6) --(CH 2 ) 3 --CH═C(CH 3 ) 2 , ##STR24## (1) (C 4 -C 7 )cycloalkyl optionally substituted by one to 3 (C 1 -C 5 )alkyl, (2) 3-thienyloxymethyl, ##STR25## (4) --C.tbd.C--C q H 2 .sbsb.q CH 3 wherein q is an integer of from 2 to 6, or (5) --C p H 2 .sbsb.p CH═CH 2 wherein p is an integer of from 3 to 7; and individual optical isomers thereof.