US4558142A
Expired / Lapsed
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7-Fluoro-prostacyclin analogs
Assignee: Hoffmann La Roche Inc
•
Filing: 1982-09-07
•
Granted: 1985-12-10
•
Expires: 2002-09-07
Abstract
Abstract The prostacyclins 7-fluoro-6,9-epoxy-16-substituted-15-hydroxyprost-[4 or 5,13]-dienoic acids and esters useful as anti-secretory agents, blood pressure lowering agents, anti-ulcerogenic agents, anti-hypertensive agents, bronchodilation agents and for combating gastro-hyperacidity and as anti-blood platelet aggregating agents.
Inventors
- 👤 George W. Holland
- 👤 Perry Rosen
- 👤 Hans Maag
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 13:03
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/77; C07D307/93; C07D307/935; C07D307/937; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804
Claims Analysis
Total Claims: 60
Claim 1
Independent Claim
62 words
A compound of the formula ##STR7## wherein R is hydrogen or lower alkyl, R 1 is methyl, hydrogen, or hydroxy; R 2 is hydrogen, methyl or fluoro; and R 2 ' is hydrogen, fluoro, trifluoromethyl or methyl; with the proviso that when R 2 ' is trifluoromethyl, R 2 is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes or racemates.
Claim 2
Dependent Claim
62 words
A compound of the formula ##STR7## wherein R is hydrogen or lower alkyl, R 1 is methyl, hydrogen, or hydroxy; R 2 is hydrogen, methyl or fluoro; and R 2 ' is hydrogen, fluoro, trifluoromethyl or methyl; with the proviso that when R 2 ' is trifluoromethyl, R 2 is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes or racemates.
Claim 3
Dependent Claim
10 words
The compound of claim 1 where R 1 is hydroxy.
Claim 4
Dependent Claim
10 words
The compound of claim 2 wherein R 2 is methyl.
Claim 5
Dependent Claim
20 words
The compound of claim 3 wherein said compound is [5Z,9α,11α,13E,15R]-7-fluoro-6,9-epoxy-11,15-dihydroxy-16-methyl-prosta-5,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
Claim 6
Dependent Claim
20 words
The compound of claim 3 wherein said compound is (5Z,7β,9α,11α,13E,15R)-7-fluoro-6,9-epoxy-11,15-dihydroxy-16,16-dimethyl-prosta-5,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
Claim 7
Dependent Claim
10 words
The compound of claim 2 wherein R 2 is fluoro.
Claim 8
Dependent Claim
11 words
The compound of claim 6 wherein R 2 ' is methyl.
Claim 9
Dependent Claim
16 words
The compound of claim 6 wherein said compound is (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7,16-difluoro-11,15-dihydroxyprosta-5,13-dien-1-oic acid or its pharmaceutically acceptable salts.
Claim 10
Dependent Claim
12 words
The compound of claim 8 wherein said salt is the sodium salt.
Claim 11
Dependent Claim
16 words
The compound of claim 6 wherein said compound is a lower alkyl ester of (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7,16-difluoro-11,15-dihydroxyprosta-5,13-dien-1-oic acid.
Claim 12
Dependent Claim
12 words
The compound of claim 10 wherein said ester is the methyl ester.
Claim 13
Dependent Claim
19 words
The compound of claim 6 wherein said compound is (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7,16,16-triflfuoro-11,15-di hydroxyprosta-5,13-dienoic acid, its lower alkyl esters or its salts.
Claim 14
Dependent Claim
12 words
The compound of claim 12 wherein said compound is a sodium salt.
Claim 15
Dependent Claim
12 words
The compound of claim 12 wherein said compound is a methyl ester.
Claim 16
Dependent Claim
11 words
The compound of claim 12 wherein said compound is the acid.
Claim 17
Dependent Claim
11 words
The compound of claim 2 wherein R 2 ' is trifluoromethyl.
Claim 18
Dependent Claim
18 words
The compound of claim 16 wherein said compound is (5Z,9alpha,11alpha,13E,15R)-6,9-epoxy-7-fluoro-16-trifluoromethyl-16-methyl-11,15-dihydroxyprosta-5,13-diene-1-oic acid, its lower alkyl esters or its salt.
Claim 19
Dependent Claim
11 words
The compound of claim 17 wherein said compound is the acid.
Claim 20
Dependent Claim
11 words
The compound of claim 17 wherein said compound is the salt.
Claim 21
Dependent Claim
12 words
The compound of claim 17 wherein said compound is the methyl ester.
Claim 22
Dependent Claim
14 words
The compound of claim 2 wherein R 2 and R 2 ' are hydrogen.
Claim 23
Dependent Claim
13 words
The compound of claim 21 wherein said compound is a lower alkyl ester.
Claim 24
Dependent Claim
16 words
The compound of claim 21 wherein the compound is (5Z,9S,11R,13E,15S)-11,15-dihydroxy-6,9-epoxy-7-fluoro-prosta-5,13-dien-1-oic acid and its pharmaceutically acceptable salts.
Claim 25
Dependent Claim
10 words
The compound of claim 1 wherein R 1 is hydrogen.
Claim 26
Dependent Claim
14 words
The compound of claim 24 wherein R 2 and R 2 ' are hydrogen.
Claim 27
Dependent Claim
16 words
The compound of claim 25 wherein said compound is (5Z,9alpha,13E,15S)-6,9-epoxy-7-fluoro-15-hydroxyprosta-5,13-dien-1-oic acid and its pharmaceutically acceptable salts.
Claim 28
Dependent Claim
13 words
The compound of claim 24 wherein said compound is (5Z,9α,13E,15R,16R)-7,16-difluoro-6,9-epoxy-15-hydroxy-prosta-5,13-dien-1-oic acid methyl ester.
Claim 29
Dependent Claim
15 words
The compound of claim 24 wherein said compound is the sodium salt of (5Z,9α,13E,15R,16R)-7,16-difluoro-15-hydroxy-6,9-epoxy-prosta-5,13-dien-1-oic acid.
Claim 30
Dependent Claim
10 words
The compound of claim 24 wherein R 2 is methyl.
Claim 31
Dependent Claim
16 words
The compound of claim 29 wherein said compound is (5Z,9alpha,13E,15R)-6,9-epoxy-7-fluoro-16,16-dimethyl-15-hydroxyprosta-5,13-dien-1-oic acid and its pharmaceutically acceptable salts.
Claim 32
Dependent Claim
10 words
The compound of claim 29 wherein R 2 is trifluoromethyl.
Claim 33
Dependent Claim
10 words
The compound of claim 1 wherein R 1 is methyl.
Claim 34
Dependent Claim
10 words
The compound of claim 32 wherein R 2 is hydrogen.
Claim 35
Dependent Claim
11 words
The compound of claim 33 wherein R 2 ' is hydrogen.
Claim 36
Dependent Claim
11 words
The compound of claim 33 wherein R 2 ' is fluoro.
Claim 37
Dependent Claim
10 words
The compound of claim 32 wherein R 2 is methyl.
Claim 38
Dependent Claim
11 words
The compound of claim 36 wherein R 2 ' is trifluoromethyl.
Claim 39
Dependent Claim
11 words
The compound of claim 36 wherein R 2 ' is fluoro.
Claim 40
Dependent Claim
11 words
The compound of claim 36 wherein R 2 ' is methyl.
Claim 41
Dependent Claim
10 words
The compound of claim 32 wherein R 2 is fluoro.
Claim 42
Dependent Claim
11 words
The compound of claim 40 wherein R 2 ' is hydrogen.
Claim 43
Dependent Claim
63 words
A compound of the formula: ##STR8## wherein R is hydrogen or lower alkyl, R 1 is methyl, hydrogen, or hydroxy; R 2 is hydrogen, methyl or fluoro; and R 2 ' is hydrogen, fluoro, trifluoromethyl or methyl; and with the proviso that when R 2 ' is trifluoromethyl, R 2 is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes or racemates.
Claim 44
Dependent Claim
63 words
A compound of the formula: ##STR8## wherein R is hydrogen or lower alkyl, R 1 is methyl, hydrogen, or hydroxy; R 2 is hydrogen, methyl or fluoro; and R 2 ' is hydrogen, fluoro, trifluoromethyl or methyl; and with the proviso that when R 2 ' is trifluoromethyl, R 2 is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes or racemates.
Claim 45
Dependent Claim
9 words
The compound of claim 42 where R is hydroxy.
Claim 46
Dependent Claim
20 words
The compound of claim 43 wherein said compound is [4E,6α,9α,11α,13E,15R]-7-fluoro-6,9-epoxy-11,15-dihydroxy-16-dimethyl-prosta-4,13-dien-1-oic acid, its pharmaceutically acceptable salts, or its lower alkyl esters.
Claim 47
Dependent Claim
20 words
The compound of claim 43 wherein said compound is [4E,6α,7β,9α,11α,13E,15R]-7-fluoro-6,9-epoxy-11,15-dihydroxyprost-4,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
Claim 48
Dependent Claim
10 words
The compound of claim 42 wherein R 1 is hydrogen.
Claim 49
Dependent Claim
20 words
The compound of claim 46 wherein said compound is (4E,9α,13E,15R,16R)-7,16-difluoro-6,9-epoxy-15-hydroxy-prosta-4,13-dien-1-oic acid, its pharmaceutically acceptable salts or its lower alkyl esters.
Claim 50
Dependent Claim
76 words
The compound of the formula: ##STR9## wherein R 6 is lower alkyl; R 1 ' is hydrogen, methyl or --OR 5 , R 2 is methyl, hydrogen or fluoro; R 2 ' is fluoro, hydrogen, trifluoromethyl or methyl; and X is halogen; --OR 5 is hydroxy or forms an acid hydrolyzable ether protecting group with the proviso that when R 2 ' is trifluoromethyl; R 2 is hydrogen or methyl; or their optical antipodes or racemates.
Claim 51
Dependent Claim
76 words
The compound of the formula: ##STR9## wherein R 6 is lower alkyl; R 1 ' is hydrogen, methyl or --OR 5 , R 2 is methyl, hydrogen or fluoro; R 2 ' is fluoro, hydrogen, trifluoromethyl or methyl; and X is halogen; --OR 5 is hydroxy or forms an acid hydrolyzable ether protecting group with the proviso that when R 2 ' is trifluoromethyl; R 2 is hydrogen or methyl; or their optical antipodes or racemates.
Claim 52
Dependent Claim
13 words
The compound of claim 48 wherein R 1 ' is --OR 5 .
Claim 53
Dependent Claim
13 words
The compound of claim 49 wherein said compound is (7β,9α,11α,13E,15R)-16,16-dimethyl-11,15-di[(tetrahydro-2H-pyran-2-yl)oxy]-6,9-epoxy-7-fluoro-5-iodo-prosta-13-en-1-oic acid methyl ester.
Claim 54
Dependent Claim
13 words
The compound of claim 49 wherein said compound is (7β,9α,11α,13E,15R)-16,16-dimethyl-11,15-dihydroxy-6,9-epoxy-7-fluoro-5-iodo-prosta-13-en-1-oic acid methyl ester.
Claim 55
Dependent Claim
11 words
The compound of claim 48 wherein R 1 ' is hydrogen.
Claim 56
Dependent Claim
13 words
The compound of claim 52 wherein said compound is (9α,13E,15R,16R)-7,16-difluoro-15-hydroxy-6,9-epoxy-5-iodo-prosta-13-en-1-oic acid methyl ester.
Claim 57
Dependent Claim
36 words
A compound of the formula ##STR10## wherein R is hydrogen or lower alkyl; R 2 is hydrogen or methyl and R 2 ' is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes and racemates.
Claim 58
Dependent Claim
36 words
A compound of the formula ##STR10## wherein R is hydrogen or lower alkyl; R 2 is hydrogen or methyl and R 2 ' is hydrogen or methyl or their pharmaceutically acceptable salts, optical antipodes and racemates.
Claim 59
Dependent Claim
46 words
A compound of the formula ##STR11## wherein R 6 is lower alkyl; R 2 is methyl or hydrogen; R 2 ' is hydrogen or methyl; X is halogen; OR 5 is hydroxy or forms an acid hydrolyzable ether protecting group or their optical antipodes or racemates.
Claim 60
Dependent Claim
46 words
A compound of the formula ##STR11## wherein R 6 is lower alkyl; R 2 is methyl or hydrogen; R 2 ' is hydrogen or methyl; X is halogen; OR 5 is hydroxy or forms an acid hydrolyzable ether protecting group or their optical antipodes or racemates.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-12-09 | 1989-06-10 | 1989-12-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-12-09 | 1993-06-10 | 1993-12-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-12-09 | 1997-06-10 | 1997-12-10 | $7700.00 | Window Closed / Lapsed |