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US4351846A
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3-Hydroxy and 3-oxo-prostaglandin analogues
Assignee: Ono Pharmaceutical Co Ltd
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Filing: 1981-05-08
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Granted: 1982-09-28
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Expires: 2001-05-08
Abstract
Abstract Prostaglandin analogues of the formula: ##STR1## [wherein R 1 represents hydrogen or alkyl of 1 to 12 carbon atoms, R 2 represents a single bond or alkylene of from 1 to 5 carbon atoms, R 3 represents hydrogen, alkyl or alkoxy of 1 to 8 carbon atoms, cycloalkyl or cycloalkyloxy of 4 to 7 carbon atoms unsubstituted or substituted by alkyl of 1 to 8 carbon atoms, or phenyl or phenoxy unsubstituted or substituted by halogen, trifluoromethyl or alkyl of 1 to 4 carbon atoms, one of R 4 and R 5 represents hydrogen and the other represents hydroxy or R 4 and R 5 together represent oxo, R 6 represents hydrogen or a hydroxy-protecting group which may be removed under acidic conditions, the double bond between the carbon atoms in positions 13 and 14 is trans, the wavy line attached to the carbon atom in position 15 represents α- or β- configuration or a mixture thereof and, when one of R 4 and R 5 represents hydrogen and the other represents hydroxy, the configuration of the carbon atom in position 3 is R-- or S or a mixture thereof, provided that, when R 2 represents a single bond, R 3 does not represent alkoxy, cycloalkyloxy or phenoxy and when R 6 represents a hydrogen atom, cyclodextrin clathrates thereof and, when R 1 represents a hydrogen atom, non-toxic salts thereof, possess selective prostaglandin-like properties.
Inventors
- 👤 Kimiichiro Matsumoto
- 👤 Hajimu Miyake
- 👤 Hisashi Suga
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 12:33
CPC Classifications
B; B82; B82Y; B82Y5/00; A; A61; A61K; A61K47/00; A61K47/50; A61K47/69; A61K47/6949; A61K47/6951; A61P; A61P43/00; C; C07; C07C; C07C405/00; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
286 words
A prostaglandin analogue of the formula: ##STR13## (wherein R 1 represents a hydrogen atom or an alkyl group containing from 1 to 12 carbon atoms, R 2 represents a single bond or an alkylene group containing from 1 to 5 carbon atoms, R 3 represents a hydrogen atom, an alkyl or alkoxy group containing from 1 to 8 carbon atoms, a cycloalkyl or cycloalkyloxy group containing from 4 to 7 carbon atoms and being unsubstituted or substituted by at least one alkyl group containing from 1 to 8 carbon atoms, or a phenyl or phenoxy group unsubstituted or substituted by at least one halogen atom, trifluoromethyl group or alkyl group containing from 1 to 4 carbon atoms, one of R 4 and R 5 represents a hydrogen atom and the other represents a hydroxy group or R 4 and R 5 together represent an oxo group, R 6 represents a hydrogen atom or a hydroxy-protecting group which may be removed under mild acidic conditions, the double bond between the carbon atoms in positions 13 and 14 is in trans configuration, the wavy line attached to the carbon atom in position 15 represents α- or β-configuration or a mixture thereof and, when one of R 4 and R 5 represents a hydrogen atom and the other represent a hydroxy group, the configuration of the carbon atom in position 3 is R or S or a mixture thereof, provided that, when R 2 represents a single bond, R 3 does not represent an alkoxy group, a cycloalkyloxy group or a phenoxy group) or when R 6 represents a hydrogen atom, a cyclodextrin clathrate thereof or, when R 1 and R 6 represent hydrogen atoms, a non-toxic salt thereof.
Claim 2
Dependent Claim
286 words
A prostaglandin analogue of the formula: ##STR13## (wherein R 1 represents a hydrogen atom or an alkyl group containing from 1 to 12 carbon atoms, R 2 represents a single bond or an alkylene group containing from 1 to 5 carbon atoms, R 3 represents a hydrogen atom, an alkyl or alkoxy group containing from 1 to 8 carbon atoms, a cycloalkyl or cycloalkyloxy group containing from 4 to 7 carbon atoms and being unsubstituted or substituted by at least one alkyl group containing from 1 to 8 carbon atoms, or a phenyl or phenoxy group unsubstituted or substituted by at least one halogen atom, trifluoromethyl group or alkyl group containing from 1 to 4 carbon atoms, one of R 4 and R 5 represents a hydrogen atom and the other represents a hydroxy group or R 4 and R 5 together represent an oxo group, R 6 represents a hydrogen atom or a hydroxy-protecting group which may be removed under mild acidic conditions, the double bond between the carbon atoms in positions 13 and 14 is in trans configuration, the wavy line attached to the carbon atom in position 15 represents α- or β-configuration or a mixture thereof and, when one of R 4 and R 5 represents a hydrogen atom and the other represent a hydroxy group, the configuration of the carbon atom in position 3 is R or S or a mixture thereof, provided that, when R 2 represents a single bond, R 3 does not represent an alkoxy group, a cycloalkyloxy group or a phenoxy group) or when R 6 represents a hydrogen atom, a cyclodextrin clathrate thereof or, when R 1 and R 6 represent hydrogen atoms, a non-toxic salt thereof.
Claim 3
Dependent Claim
14 words
A prostaglandin analogue according to claim 1 wherein R 6 represents a hydrogen atom.
Claim 4
Dependent Claim
28 words
A prostaglandin analogue according to claim 1 wherein R 1 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms.
Claim 5
Dependent Claim
18 words
A prostaglandin analogue according to claim 1 wherein R 1 represents a hydrogen atom or a methyl group.
Claim 6
Dependent Claim
82 words
A prostaglandin analogue according to claim 1 wherein the grouping --R 2 --R 3 represents n-pentyl or n-hexyl unsubstituted or substituted by one or two methyl group(s), or R 2 represents a single bond or a methylene or ethylene group and R 3 represents a cyclopentyl or cyclohexyl group unsubstituted or substituted by an alkyl group containing from 1 to 4 four carbon atoms, or a phenyl or phenoxy group unsubstituted or substituted by at least one halogen atom or trifluoromethyl group.
Claim 7
Dependent Claim
39 words
A prostaglandin analogue according to claim 1 wherein the grouping --R 2 --R 3 represents n-pentyl, 1-methylpentyl, 2-methylpentyl, 1,1-dimethylpentyl, n-hexyl, 2-methylhexyl, cyclopentyl, cyclopentylmethyl, 2-cyclopentylethyl, 3-ethylcyclopentyl, 3-propylcyclopentyl, 3-butylcyclopentyl, cyclohexyl, cyclohexylmethyl, 2-cyclohexylethyl, 4-methylcyclohexyl, 4-propylcyclohexyl, benzyl, 2-phenylethyl, phenoxymethyl, 3-chlorophenoxymethyl, 4-chlorophenoxymethyl or 3-trifluoromethylphenoxymethyl.
Claim 8
Dependent Claim
16 words
A prostaglandin analogue according to claim 1 wherein the grouping --R 2 --R 3 represents 1,1-dimethylpentyl.
Claim 9
Dependent Claim
28 words
A prostaglandin analogue according to claim 1 wherein the group OR 6 attached to the C-15 carbon atoms in formula IV depicted in claim 1 is in α-configuration.
Claim 10
Dependent Claim
17 words
A compound according to claim 1 which is (13E)-(11α,15R)-3,9-dioxo-11,15-dihydroxy-16,16-dimethylprost-13-enoic acid methyl ester or a cyclodextrin clathrate thereof.
Claim 11
Dependent Claim
17 words
A compound according to claim 1 which is (13E)-(11α,15R)-3,9-dioxo-11,15-dihydroxy-16,16-dimethylprost-13-enoic acid tert-butyl ester or a cyclodextrin clathrate thereof.
Claim 12
Dependent Claim
18 words
A compound according to claim 1 which is (13E)-(3RS,11α,15R)-3,11,15-trihydroxy-9-oxo-16,16-dimethylprost-13-enoic acid or a cyclodextrin clathrate or non-toxic salt thereof.
Claim 13
Dependent Claim
35 words
A compound according to claim 1 which is a non-toxic salt of a prostaglandin analogue as claimed in any one of claims 1 to 8 wherein R 1 and R 6 both represent hydrogen atoms.
Claim 14
Dependent Claim
32 words
A compound according to claim 1 which is a cyclodextrin clathrate of a prostaglandin analogue as claimed in any one of claims 1 to 8 wherein R 6 represents a hydrogen atom.
Claim 15
Dependent Claim
84 words
A pharmaceutical composition useful in the termination of pregnancy or induction of labour in pregnant female mammals and in contraception and menstrual regulation in female mammals which comprises an effective amount of at least one compound of general formula IV claimed in claim 1, wherein R 6 represents a hydrogen atom and the other symbols are as defined in claim 1, or cyclodextrin clathrate thereof, or when R 1 represents a hydrogen atom, non-toxic salt thereof, in association with a pharmaceutical carrier or coating.
Claim 16
Dependent Claim
38 words
A pharmaceutical composition according to claim 14 in which the active ingredient is (13E)-(11α,15R)-3,9-dioxo-11,15-dihydroxy-16,16-dimethylprost-13-enoic acid methyl ester or (13E)-(11α,15R)-3,9-dioxo-11,15-dihydroxy-16,16-dimethylprost-13-enoic acid tert-butyl ester or a cyclodextrin clathrate thereof, or (13E)-(3RS,11α,15R)-3,11,15-trihydroxy-9-oxo-16,16-dimethylprost-13-enoic acid or a non-toxic salt or cyclodextrin clathrate thereof.
Claim 17
Dependent Claim
79 words
A method for the termination of pregnancy or induction of labour in a pregnant female mammal or for contraception or menstrual regulation in a female mammal which comprises administering an effective amount of a compound of general formula IV claimed in claim 1 wherein R 6 represents a hydrogen atom, and the other symbols are as defined in claim 1, or of a cyclodextrin clathrate thereof or, when R 1 represents a hydrogen atom, of a nontoxic salt thereof.
Claim 18
Dependent Claim
32 words
A prostaglandin analogue according to claim 1 wherein R 6 represents a hydroxy-protecting group which may be removed under mild acidic conditions and the other symbols are as defined in claim 1.
Claim 19
Dependent Claim
12 words
A compound according to claim 1 which is (13E)-(11α,15R)-3,9-dioxo-11,15-bis(tetrahydropyran-2-yloxy)-16,16-dimethylprost-13-enoic acid methyl ester.
Claim 20
Dependent Claim
12 words
A compound according to claim 1 which is (13E)-(11α,15R)-3,9-dioxo-11,15-bis(tetrahydropyran-2-yloxy)-16,16-dimethylprost-13-enoic acid tert-butyl ester.
Claim 21
Dependent Claim
12 words
A compound according to claim 1 which is (13E)-(3RS,11α,15R)-3-hydroxy-9-oxo-11,15-bis(tetrahydropyran-2-yloxy)-16,16-dimethylprost-13-enoic acid methyl ester.
Claim 22
Dependent Claim
12 words
A compound according to claim 1 which is (13E)-(3RS,11α,15R)-3-hydroxy-9-oxo-11,15-bis(tetrahydropyran-2-yloxy)-16,16-dimethylprost-13-enoic acid tert-butyl ester.
Claim 23
Dependent Claim
10 words
A compound according to claim 1 which is (13E)-(3RS,11α,15R)-3-hydroxy-9-oxo-11,15-bis(tetrahydropyran-2-yloxy)-16,16-dimethylprost-13-enoic acid.
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) | 1985-09-27 | 1986-03-29 | 1986-09-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-09-27 | 1990-03-29 | 1990-09-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-09-27 | 1994-03-29 | 1994-09-28 | $7700.00 | Window Closed / Lapsed |