US4205178A
Expired / Lapsed
US
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6-Keto prostaglandin E-type compounds
Assignee: Pharmacia and Upjohn Co
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Filing: 1977-09-02
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Granted: 1980-05-27
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Expires: 1997-09-02
Abstract
Abstract Prostaglandin E (PGE)-type derivatives and analogs having a 6-keto feature are disclosed, including processes for preparing them and the appropriate intermediates, said derivatives having pharmacological activity. A typical 6-keto compound is 6-keto-PGE 1 , methyl ester, represented by the formula: ##STR1##
Inventors
- 👤 Udo F. Axen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 10:34
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/77; C07D307/93; C07D307/935; C07D307/937; C07C; C07C405/00; C07C405/0008; C07C405/0025; C07C405/0041
Claims Analysis
Total Claims: 45
Claim 1
Independent Claim
287 words
A compound of the formula ##STR144## or a mixture comprising that compound and the enantiometer thereof wherein D is (1) --(CH 2 ) 3 --C(R 2 ) 2 -- (2) --CH 2 --O--CH 2 --Y-- or (3) --CH 2 CH═CH-- wherein d is zero to 5, R 2 is hydrogen, methyl, or fluoro, being the same or different with the proviso that one R 2 is not methyl when the other is fluoro, and Y is a valence bond, --CH 2 -- or --(CH 2 ) 2 --, wherein Q is ##STR145## wherein R 8 is hydrogen, methyl, or ethyl, 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 of one to 4 carbon atoms, inclusive, ##STR146## wherein R 10 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, and wherein R 11 is hydrogen or benzoyl, or (n) a pharmacologically acceptable cation, wherein R 18 is ##STR147## wherein R 38 is ##STR148## wherein C g H 2g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR 5 R 6 -- and terminal methyl, 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-- (4) --CH 2 CH 2 --, including the lower alkanoates thereof.
Claim 2
Dependent Claim
287 words
A compound of the formula ##STR144## or a mixture comprising that compound and the enantiometer thereof wherein D is (1) --(CH 2 ) 3 --C(R 2 ) 2 -- (2) --CH 2 --O--CH 2 --Y-- or (3) --CH 2 CH═CH-- wherein d is zero to 5, R 2 is hydrogen, methyl, or fluoro, being the same or different with the proviso that one R 2 is not methyl when the other is fluoro, and Y is a valence bond, --CH 2 -- or --(CH 2 ) 2 --, wherein Q is ##STR145## wherein R 8 is hydrogen, methyl, or ethyl, 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 of one to 4 carbon atoms, inclusive, ##STR146## wherein R 10 is phenyl, p-bromophenyl, p-biphenylyl, p-nitrophenyl, p-benzamidophenyl, or 2-naphthyl, and wherein R 11 is hydrogen or benzoyl, or (n) a pharmacologically acceptable cation, wherein R 18 is ##STR147## wherein R 38 is ##STR148## wherein C g H 2g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR 5 R 6 -- and terminal methyl, 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-- (4) --CH 2 CH 2 --, including the lower alkanoates thereof.
Claim 3
Dependent Claim
11 words
A compound according to claim 1 wherein R 18 is ##STR149##
Claim 4
Dependent Claim
16 words
A compound according to claim 2 wherein D is --(CH 2 )d--C(R 2 ) 2 --.
Claim 5
Dependent Claim
14 words
A compound according to claim 3 wherein D is --(CH 2 ) 3 --.
Claim 6
Dependent Claim
10 words
A compound according to claim 4 wherein X is trans--CH═CH--.
Claim 7
Dependent Claim
10 words
A compound according to claim 5 wherein Q is ##STR150##
Claim 8
Dependent Claim
9 words
6,15-Diketo-PGE 1 , a compound according to claim 6.
Claim 9
Dependent Claim
18 words
A compound according to claim 5 wherein Q is ##STR151## wherein R 8 is hydrogen, methyl or ethyl.
Claim 10
Dependent Claim
11 words
A compound according to claim 8 wherein R 8 is hydrogen.
Claim 11
Dependent Claim
11 words
6-Keto-PGE 1 , methyl ester, a compound according to claim 9.
Claim 12
Dependent Claim
9 words
6-Keto-PGE 1 , a compound according to claim 9.
Claim 13
Dependent Claim
11 words
6-Keto-PGE 1 , sodium salt, a compound according to claim 9.
Claim 14
Dependent Claim
11 words
6-Keto-PGE 1 , p-phenylphenacyl ester a compound according to claim 9.
Claim 15
Dependent Claim
11 words
6-Keto-PGE 1 , p-(p-acetamidobenzamido)phenyl ester, a compound according to claim 9.
Claim 16
Dependent Claim
12 words
6-Keto-PGE 1 , p-benzaldehyde semicarbazone ester, a compound according to claim 9.
Claim 17
Dependent Claim
9 words
16,16-Dimethyl-6-keto-PGE 1 , a compound according to claim 9.
Claim 18
Dependent Claim
11 words
16,16-Dimethyl-6-keto-PGE 1 , p-phenylphenacyl ester, a compound according to claim 9.
Claim 19
Dependent Claim
11 words
16,16-Dimethyl-6-keto-PGE 1 , p-(p-acetamidobenzamido)phenyl ester, a compound according to claim 9.
Claim 20
Dependent Claim
12 words
16,16-Dimethyl-6-keto-PGE 1 , p-benzaldehyde semicarbazone ester, a compound according to claim 9.
Claim 21
Dependent Claim
11 words
A compound according to claim 8 wherein R 8 is methyl.
Claim 22
Dependent Claim
9 words
15(S)-15-Methyl-6-keto-PGE 1 , a compound according to claim 20.
Claim 23
Dependent Claim
11 words
15(S)-15-Methyl-6-keto-PGE 1 , p-phenylphenacyl ester, a compound according to claim 20.
Claim 24
Dependent Claim
11 words
15(S)-15-Methyl-6-keto-PGE 1 , p-(p-acetamidobenzamido)phenyl ester, a compound according to claim 20.
Claim 25
Dependent Claim
12 words
15(S)-15-Methyl-6-keto-PGE 1 , benzaldehyde semicarbazone ester, a compound according to claim 20.
Claim 26
Dependent Claim
18 words
A compound according to claim 5 wherein Q is ##STR152## wherein R 8 is hydrogen, methyl, or ethyl.
Claim 27
Dependent Claim
9 words
(15R)-15-Methyl-6-keto-PGE 1 , a compound according to claim 25.
Claim 28
Dependent Claim
10 words
A compound according to claim 4 wherein X is --C.tbd.C--.
Claim 29
Dependent Claim
18 words
A compound according to claim 27 wherein Q is ##STR153## wherein R 8 is hydrogen, methyl, or ethyl.
Claim 30
Dependent Claim
9 words
6-Keto-13,14-didehydro-PGE 1 , a compound according to claim 28.
Claim 31
Dependent Claim
18 words
A compound according to claim 27 wherein Q is ##STR154## wherein R 8 is hydrogen, methyl, or ethyl.
Claim 32
Dependent Claim
9 words
6-Keto-13,14-didehydro-(15R)-PGE 1 , a compound according to claim 30.
Claim 33
Dependent Claim
15 words
A compound according to claim 4 wherein wherein X is --CH 2 CH 2 --.
Claim 34
Dependent Claim
9 words
6-Keto-13,14-dihydro-PGE 1 , a compound according to claim 32.
Claim 35
Dependent Claim
16 words
A compound according to claim 3 wherein D is --(CH 2 ) 2 --CF 2 --.
Claim 36
Dependent Claim
10 words
A compound according to claim 34 wherein X is trans-CH═CH--.
Claim 37
Dependent Claim
10 words
A compound according to claim 35 wherein Q is ##STR155##
Claim 38
Dependent Claim
11 words
2,2-Difluoro-6-keto-PGE 1 , methyl ester, a compound according to claim 36.
Claim 39
Dependent Claim
11 words
2,2-Difluoro-16,16-dimethyl-6-keto-PGE 1 , methyl ester, a compound according to claim 36.
Claim 40
Dependent Claim
10 words
A compound according to claim 35 wherein Q is ##STR156##
Claim 41
Dependent Claim
11 words
2,2-Difluoro-(15S)-15-methyl-6-keto-PGE 1 , methyl ester, a compound according to claim 39.
Claim 42
Dependent Claim
10 words
A compound according to claim 34 wherein X is --C.tbd.C--.
Claim 43
Dependent Claim
11 words
2,2-Difluoro-13,14-didehydro-6-keto-PGE 1 , methyl ester, a compound according to claim 41.
Claim 44
Dependent Claim
14 words
A compound according to claim 34 wherein X is --CH 2 CH 2 --.
Claim 45
Dependent Claim
11 words
2,2-Difluoro-13,14-dihydro-6-keto-PGE 1 , methyl ester, a compound according to claim 43.
References Cited (Backward Citations)
DE2509415A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-05-27 | 1983-11-26 | 1984-05-27 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-05-27 | 1987-11-26 | 1988-05-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-05-27 | 1991-11-26 | 1992-05-27 | $7700.00 | Window Closed / Lapsed |