US 4,292,438 AGrant
13,14-Didehydro-9-deoxy-9-methylene-19-oxo-PGF.sub.2 Compounds
Issue Date:1981-09-29
•4 Claims
Abstract
The present invention provides novel 13,14-didehydro-9-deoxy-9-methylene-19-oxo-PGF.sub.2 compounds, which are useful for a variety of pharmacological purposes, e.g., antiasthmatic indications.
Metadata
Assignee
- The Upjohn Company
Inventor
- John C. Sih
Application Information
Application Number:US 1319620
Filing Date:1980-03-20
Priority Date:1979-04-02
Art Unit:126
Classifications
IPC:
C07C17700
Field of Search:
560562260121503404;404.5;408;410;410.5;410.9 R;413
Patent Drawings
This patent does not have any drawings.
Description
Background of the Invention
The present invention relates to novel prostaglandin analogs. Particularly, the invention relates to prostaglandin analogs wherein the C-19 position is substituted by oxo, i.e., 19-keto-PG compounds or 19-oxo-PG compounds. Most particularly, the present invention relates to novel 13,14-Didehydro-9-deoxy-9-methylene-19-oxo-PGF.sub.2 compounds, a disclosure of the preparation and pharmacological use of which is incorporated here by reference from U.S. Ser. No. 025,899, filed Apr. 2, 1979.
Prior Art
Prostaglandins exhibiting a variety of substitution at the C-19 position are known. See particularly J. C. Sih, et al., JACS 91:3685 (1969) wherein 19-oxo-PGE.sub.2 and 13,14-dihydro-19-oxo-PGE.sub.1 are disclosed. Further, Chemical Abstracts 86:43265H purportedly discloses 19-oxo-PGF.sub.2 .alpha.. The abstract is derived from Japanese Kokai No. 76 82,245.
Summary of the Invention
The present invention particularly provides:
a compound of the formula ##STR1## wherein D is (1) cis--CH.dbd.CH--CH.sub.2 --(CH.sub.2).sub.g --CH.sub.2 --,
(2) cis--CH.dbd.CH--CH.sub.2 --(CH.sub.2).sub.g --CF.sub.2 --,
(3) cis--CH.sub.2 --CH.dbd.CH--CH.sub.2 --CH.sub.2 --, or
(4) trans--(CH.sub.2).sub.3 --CH.dbd.CH--;
wherein g is zero, one, two, or three;
wherein Q is .alpha.--OH:.beta.--R.sub.5 or .alpha.--R.sub.5 :.beta.--OH, wherein R.sub.5 is hydrogen or methyl;
wherein R.sub.6 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) --(p--Ph)--CO--CH.sub.3,
(h) --(p--Ph)--NH--CO--(p--Ph)--NH--CO--CH.sub.3,
(i) --(p--Ph)--NH--CO--(p--Ph),
(j) --(p--Ph)--NH--CO--CH.sub.3,
(k) --(p--Ph)--NH--CO--NH.sub.2,
(l) --(p--Ph)--CH.dbd.N--NH--CO--NH.sub.2,
(m) .beta.-naphthyl,
(n) --CH.sub.2 --CO--R.sub.28,
wherein (p--Ph) is para-phenyl or inter-para-phenylene,
wherein R.sub.28 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, or
(o) a pharmacologically acceptable cation;
wherein R.sub.3 and R.sub.4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R.sub.3 and R.sub.4 is fluoro only when the other is hydrogen or fluoro; and
wherein X is --C.tbd.C--.
The compounds of the present invention are particularly useful for inducing prostaglandin-like biological effects, as described in U.S. Ser. No. 026,066. Uses of compounds in accordance with the present invention include, therefore, antiasthmatic indications.
Description of the Preferred Embodiments
The present invention particularly relates to:
13,14-didehydro-9-deoxy-9-methylene-19-oxo-PGF.sub.2, and 13,14-didehydro-9-deoxy-9-methylene-(15R)-19-oxo-PGF.sub.2.
Claims
I claim:
1. A compound of the formula ##STR2## wherein D is (1) cis--CH.dbd.CH--CH.sub.2 --(CH.sub.2).sub.g --CH.sub.2 --, (2) cis--CH.dbd.CH--CH.sub.2 --(CH.sub.2).sub.g --CF.sub.2 --, (3) cis--CH.sub.2 --CH.dbd.CH--CH.sub.2 --CH.sub.2 --, or (4) trans--(CH.sub.2).sub.3 --CH.dbd.CH--; wherein g is zero, one, two, or three; wherein Q is .alpha.--OH:.beta.--R.sub.5 or .alpha.--R.sub.5 :.beta.--OH, wherein R.sub.5 is hydrogen or methyl; wherein R.sub.6 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) --(p--Ph)--CO--CH.sub.3, (h) --(p--Ph)--NH--CO--(p--Ph)--NH--CO--CH.sub.3, (i) --(p--Ph)--NH--CO--(p--Ph), (j) --(p--Ph)--NH--CO--CH.sub.3, (k) --(p--Ph)--NH--CO--NH.sub.2, (l) --(p--Ph)--CH.dbd.N--NH--CO--NH.sub.2, (m) .beta.-naphthyl, (n) --CH.sub.2 --CO--R.sub.28, wherein (p--Ph) is para-phenyl or inter-para-phenylene, wherein R.sub.28 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, or (o) a pharmacologically acceptable cation; wherein R.sub.3 and R.sub.4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R.sub.3 and R.sub.4 is fluoro only when the other is hydrogen or fluoro; and wherein X is --C.tbd.C--.
2. A compound according to claim 1, wherein R.sub.6 is hydrogen or methyl.
3. 13,14-Didehydro-9-deoxy-9-methylene-19-oxo-PGF.sub.2, a compound according to claim 2.
4. 13,14-Didehydro-9-deoxy-9-methylene-15(R)-19-oxo-PGF.sub.2, a compound according to claim 2.
Patent Citations (1)
| Patent | Date | Inventor | Cited By |
|---|---|---|---|
| US4054575 | 1977-10-01 | Marx et al. |