Enlarged-hetero-ring prostacyclin analogs
AssigneeThe Upjohn Company
InventorRoy A. Johnson
Life of this patent
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Abstract
Prostaglandin (PG.sub.1) derivatives having (1) a 5-keto feature, for example ##STR1## or (2) a 9-deoxy-5,9-epoxy feature together with a 4-halo or 5-hydroxy feature, for example ##STR2## or a 4,5-didehydro feature, for example in an enol ether of the formula ##STR3## said derivatives having pharmacological activity. Processes for preparing them and the appropriate intermediates are disclosed.
Claims22
A 4Z compound of formula ##STR110## wherein L is --(CH.sub.2).sub.d --C (R.sub.2).sub.2 -- wherein d is zero to 5, R.sub.2 is hydrogen, methyl, or fluoro, being the same or different with the proviso that one R.sub.2 is not methyl when the other is fluoro,
- wherein Q is ##STR111## wherein R.sub.8 is hydrogen or alkyl of one to 4 carbon atoms, inclusive, wherein R.sub.59 is (a) hydrogen, (b) alkyl of one to 12 carbon atoms, inclusive,
- or (c) a pharmacologically acceptable cation;
- wherein R.sub.4 is ##STR112## wherein C.sub.g H.sub.2g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR.sub.5 R.sub.6 -- and terminal methyl, wherein R.sub.5 and R.sub.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.sub.5 and R.sub.6 is fluoro only when the other is hydrogen or fluoro;
- and
- wherein X is
- (1) trans--CH.dbd.CH--
- (2) cis--CH.dbd.CH--
- (3) --c.dbd.c-- or
- (4) --CH.sub.2 CH.sub.2 --;
- including the lower alkanoates thereof.
A 4E compound of the formula ##STR122## wherein L is --(CH.sub.2).sub.d --C (R.sub.2).sub.2 -- wherein d is zero to 5, R.sub.2 is hydrogen, methyl, or fluoro, being the same or different with the proviso that one R.sub.2 is not methyl when the other is fluoro,
- wherein Q is ##STR123## wherein R.sub.8 is hydrogen or alkyl of one to 4 carbon atoms, inclusive, wherein R.sub.59 is (a) hydrogen, (b) alkyl of one to 12 carbon atoms, inclusive, a pharmacologically acceptable cation;
- wherein R.sub.4 is ##STR124## wherein C.sub.g H.sub.2.sbsb.g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR.sub.5 R.sub.6 -- and terminal methyl, wherein R.sub.5 and R.sub.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.sub.5 and R.sub.6 is fluoro only when the other is hydrogen or fluoro;
- and
- wherein X is
- (1) trans--CH.dbd.CH--
- (2) cis--CH.dbd.CH--
- (3) --c.tbd.c-- or
- (4) --CH.sub.2 CH.sub.2 --;
- including the lower alkanoates thereof.
Dependencies are inferred from the claim text.