US4131738A
Expired / Lapsed
US
⏱️ 0.0 years remaining
6-Hydroxy-PGE1 compounds
Assignee: Pharmacia and Upjohn Co
•
Filing: 1977-07-05
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Granted: 1978-12-26
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Expires: 1997-07-05
Abstract
Abstract This invention relates to certain structural analogs of the prostaglandins which have been unexpectedly discovered to be pharmacological analogs of prostacyclin (PGI 2 ), i.e., they exhibit the characteristic prostacyclin-type biological responses. These novel compounds are all 6-hydroxy-PGE-type compounds. They are useful for the pharmacological purposes for which prostacyclin is used, e.g., a antithromboti agents, smooth muscle stimulators, gastric antisecretory agents, antihypertensive agents, antiasthma agents, nasal decongestants, or regulators or fertility and procreation.
Inventors
- 👤 Herman W. Smith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 10:35
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/77; C07D307/93; C07D307/935; C07D307/937; A; A61; A61P; A61P43/00; C07C; C07C405/00
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
235 words
A prostacyclin analog of the formula ##STR18## wherein Z 1 is (1) --(CH 2 ) g --CH 2 --CH 2 --, (2) --(ch 2 ) g --CH 2 --CF 2 --, or (3) trans-(CH 2 ) g --CH═CH--, wherein g is the integer one, 2, or 3; wherein Y 1 is (1) trans-CH═CH--, (2) cis-CH═CH--, (3) --ch 2 ch 2 --, (4) trans-CH═C(Hal)--, or (5) --C.tbd.C-- wherein Hal is chloro or bromo; wherein M 1 is ##STR19## wherein R 5 is hydrogen or alkyl with one to 4 carbon atoms, inclusive; wherein L 1 is ##STR20## a mixture of ##STR21## wherein R 3 and R 4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R 3 and R 4 is fluoro only when the other is hydrogen or fluoro; wherein R 1 is hydrogen; alkyl of one to 12 carbon atoms, inclusive; cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive; phenyl; phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms; phenyl substituted in the para position by ##STR22## wherein R 25 is methyl, phenyl, acetamidophenyl, benzamidophenyl, or --NH 2 ; R 26 is methyl, phenyl, --NH 2 , or methoxy; and R 27 is hydrogen or acetamido, inclusive; or a pharmacologically acceptable cation; wherein m is the integer one to 5, inclusive.
Claim 2
Dependent Claim
235 words
A prostacyclin analog of the formula ##STR18## wherein Z 1 is (1) --(CH 2 ) g --CH 2 --CH 2 --, (2) --(ch 2 ) g --CH 2 --CF 2 --, or (3) trans-(CH 2 ) g --CH═CH--, wherein g is the integer one, 2, or 3; wherein Y 1 is (1) trans-CH═CH--, (2) cis-CH═CH--, (3) --ch 2 ch 2 --, (4) trans-CH═C(Hal)--, or (5) --C.tbd.C-- wherein Hal is chloro or bromo; wherein M 1 is ##STR19## wherein R 5 is hydrogen or alkyl with one to 4 carbon atoms, inclusive; wherein L 1 is ##STR20## a mixture of ##STR21## wherein R 3 and R 4 are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R 3 and R 4 is fluoro only when the other is hydrogen or fluoro; wherein R 1 is hydrogen; alkyl of one to 12 carbon atoms, inclusive; cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive; phenyl; phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms; phenyl substituted in the para position by ##STR22## wherein R 25 is methyl, phenyl, acetamidophenyl, benzamidophenyl, or --NH 2 ; R 26 is methyl, phenyl, --NH 2 , or methoxy; and R 27 is hydrogen or acetamido, inclusive; or a pharmacologically acceptable cation; wherein m is the integer one to 5, inclusive.
Claim 3
Dependent Claim
11 words
A prostacyclin analog according to claim 1, wherein ˜OH is beta.
Claim 4
Dependent Claim
10 words
6β-Hydroxy-PGE 1 , a prostacyclin analog according to claim 2.
Claim 5
Dependent Claim
11 words
A prostacyclin analog according to claim 1, wherein ˜OH is alpha.
Claim 6
Dependent Claim
10 words
6α-Hydroxy-PGE 1 , a prostacyclin analog according to claim 4.
Claim 7
Dependent Claim
10 words
6α-Hydroxy-15-methyl-PGE 1 , a prostacyclin analog according to claim 4.
Claim 8
Dependent Claim
10 words
6α-Hydroxy-16,16-dimethyl-PGE 1 , a prostacyclin analog according to claim 4.
Claim 9
Dependent Claim
16 words
A prostacyclin analog according to claim 1, wherein ˜OH is a mixture of α-OH and β-OH.
Claim 10
Dependent Claim
12 words
A prostacyclin analog according to claim 8, wherein Y 1 is cis--CH═CH--.
Claim 11
Dependent Claim
10 words
6-Hydroxy-cis-13-PGE 1 , a prostacyclin analog according to claim 9.
Claim 12
Dependent Claim
12 words
A prostacyclin analog according to claim 8, wherein Y 1 is --C.tbd.C--.
Claim 13
Dependent Claim
10 words
6-Hydroxy-13,14-didehydro-PGE 1 , a prostacyclin analog according to claim 11.
Claim 14
Dependent Claim
12 words
A prostacyclin analog according to claim 8, wherein Y 1 is trans-CH═C(Hal)--.
Claim 15
Dependent Claim
10 words
6-Hydroxy-14-chloro-PGE 1 , a prostacyclin analog according to claim 13.
Claim 16
Dependent Claim
16 words
A prostacyclin analog according to claim 8, wherein Y 1 is --CH 2 CH 2 --.
Claim 17
Dependent Claim
10 words
6-Hydroxy-13,14-dihydro-PGE 1 , a prostacyclin analog according to claim 15.
Claim 18
Dependent Claim
12 words
A prostacyclin analog according to claim 8, wherein Y 1 is trans-CH═CH--.
Claim 19
Dependent Claim
20 words
A prostacyclin analog according to claim 17, wherein Z 1 is --(CH 2 ) g --CH 2 --CF 2 --.
Claim 20
Dependent Claim
10 words
2,2-Difluoro-6-hydroxy-15-methyl-PGE 1 , a prostacyclin analog according to claim 18.
Claim 21
Dependent Claim
16 words
A prostacyclin analog according to claim 17, wherein Z 1 is trans-(CH 2 ) g --CH═CH--.
Claim 22
Dependent Claim
10 words
trans-2,3-Didehydro-6-hydroxy-PGE 1 , a prostacyclin analog according to claim 20.
Claim 23
Dependent Claim
20 words
A prostacyclin analog according to claim 17, wherein Z 1 is --(CH 2 ) g --CH 2 --CH 2 --.
Claim 24
Dependent Claim
11 words
A prostacyclin analog according to claim 22, wherein g is one.
Claim 25
Dependent Claim
11 words
A prostacyclin analog according to claim 23, wherein m is 3.
Claim 26
Dependent Claim
12 words
A prostacyclin analog according to claim 24, wherein R 5 is methyl.
Claim 27
Dependent Claim
10 words
6-Hydroxy-15-methyl-PGE 1 , a prostacyclin analog according to claim 25.
Claim 28
Dependent Claim
12 words
A prostacyclin analog according to claim 24, wherein R 5 is hydrogen.
Claim 29
Dependent Claim
19 words
A prostacyclin analog according to claim 27, wherein at least one of R 3 and R 4 is fluoro.
Claim 30
Dependent Claim
10 words
6-Hydroxy-16,16-difluoro-PGE 1 , a prostacyclin analog according to claim 28.
Claim 31
Dependent Claim
19 words
A prostacyclin analog according to claim 27, wherein at least one of R 3 and R 4 is methyl.
Claim 32
Dependent Claim
10 words
6-Hydroxy-16,16-dimethyl-PGE 1 , a prostacyclin analog according to claim 30.
Claim 33
Dependent Claim
16 words
A prostacyclin analog according to claim 27, wherein R 3 and R 4 are both hydrogen.
Claim 34
Dependent Claim
12 words
6-Hydroxy-PGE 1 , methyl ester, a prostacyclin analog according to claim 32.
Claim 35
Dependent Claim
12 words
6-Hydroxy-PGE 1 , tris(hydroxymethyl)aminomethane salt, a prostacyclin analog according to claim 32.
Claim 36
Dependent Claim
12 words
6-Hydroxy-PGE 1 , benzamidophenyl ester, a prostacyclin analog according to claim 32.
Claim 37
Dependent Claim
10 words
6-Hydroxy-PGE 1 , a prostacyclin analog according to claim 32.
References Cited (Backward Citations)
US4045449A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-12-25 | 1982-06-26 | 1982-12-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-12-25 | 1986-06-26 | 1986-12-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-12-25 | 1990-06-26 | 1990-12-26 | $7700.00 | Window Closed / Lapsed |