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|Abstract:||The present invention relates to novel 2-decarboxy-2-tetrazolyl-4-halo-5,9-epoxy-9-deoxy-PGF.sub.1 compounds, which are intermediates useful for the preparation of corresponding 5,9.alpha.-epoxy-9-deoxy-PGF.sub.1 and 5,9-epoxy-9-deoxy-4,5-didehydro-PGF.sub.1 compounds. These end products are employed for induction of a variety of prostacyclinlike pharmacological effects. Accordingly, these end products are useful pharmacological agents for the same purposes for which prostacyclin is employed.|
|Inventor(s):||Johnson; Roy A. (Kalamazoo, MI)|
|Assignee:||The Upjohn Company (Kalamazoo, MI)|
|Filing Date:||Sep 07, 1979|
|Claims:||1. A compound of the formula ##STR2## wherein W.sub.1 is .alpha.-OH:.beta.-H, .alpha.-H:.beta.-OH, oxo, methylene, .alpha.-H:.beta.-H, .alpha.-CH.sub.2 OH:.beta.-H; |
wherein L is
(1) --(CH.sub.2).sub.d --C(R.sub.2).sub.2,
(2) --O--CH.sub.2 --Y, or
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, and Y is a valence bond, --CH.sub.2 -- or --(CH.sub.2).sub.2 --,
wherein Q is oxo, .alpha.-H:.beta.-H, .alpha.-OH:.beta.-R.sub.8 or .alpha.-R.sub.8 :.beta.-OH
wherein R.sub.8 is hydrogen or alkyl of one to 4 carbon atoms, inclusive,
wherein R.sub.4 is
(1) --CR.sub.5 R.sub.6 --C.sub.g H.sub.2g .dbd.CH.sub.3
(2) --CR.sub.5 R.sub.6 --Z--(Ph)
(3) cis--CH.sub.2 --CH.dbd.CH--CH.sub.2 CH.sub.3
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 the further proviso that neither R.sub.5 nor R.sub.6 is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C.sub.j H.sub.2j wherein C.sub.j H.sub.2j is a valence bond or alkylene of one to 9 carbon atoms, inclusive, with one to 6 carbon atoms, inclusive between CR.sub.5 R.sub.6 -- and the (Ph); wherein (Ph) is phenyl or phenyl substituted by (T)s, wherein T is alkyl of one to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR.sub.7 --, wherein R.sub.7 is alkyl of one to 4 carbon atoms, inclusive, and s is zero, one, 2, or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different;
wherein R.sub.19 is chloro, bromo, or iodo; and wherein X is
(3) --C.tbd.C-- or
(4) --CH.sub.2 CH.sub.2 --.
2. A compound according to claim 1, wherein W is .alpha.-OH:.beta.-H.
3. A compound according to claim 2, wherein L is --(CH.sub.2).sub.n --, n being 2, 3, or 4, wherein Q is oxo or .alpha.-OH:.beta.-R.sub.8 and wherein R.sub.8 is hydrogen, methyl, or ethyl, and wherein R.sub.4 is n-pentyl, 1,1-dimethylpentyl, 1,1-difluoropentyl, phenoxymethyl or phenylethyl.
4. A compound according to claim 3, wherein X is trans--CH.dbd.CH--.
5. 2-Decarboxy-2-tetrazolyl-4.xi.-iodo-9-deoxy-5.xi.,9.alpha.-epoxy- PGF.sub.1, a compound according to claim 4.
6. 2-Decarboxy-2-tetrazolyl-4.xi.-bromo-9-d eoxy-5.xi.,9.alpha.-epoxy-PGF.sub.1, a compound according to claim 4.
7. 2-Decarboxy-2-tetrazolyl-4.xi.-iodo-9-deoxy-5.xi.,9.alpha.-epoxy-1 5-keto-PGF.sub.1, a compound according to claim 4.
8. 2-Decarboxy-2-tetrazolyl-4.xi.-iodo-9-deoxy-5.x i.,9.alpha.-epoxy-15-deoxy-PGF.sub.1, a compound according to claim 4.
9. 2-Decarboxy-2-tetrazolyl-4.xi.-iodo-9-deoxy-5.xi.,9.alpha.-epoxy-17 -phenyl-18,19,20-trinor-PGF.sub.1, a compound according to claim 4.