Patent US4073934A successfully refreshed from Google Patents.
US4073934A
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Novel acetylenic prostaglandin analogs
Assignee: Bayer Pharma AG
•
Filing: 1976-04-16
•
Granted: 1978-02-14
•
Expires: 1996-04-16
Abstract
Abstract Optically active and racemic prostaglandin derivatives of the formula ##STR1## wherein R 1 is --OR 5 ; --NHSO 2 CH 3 ; or --O--CH 2 --U--V; R 5 is hydrogen, alkyl, aryl, or a heterocyclic group; U is a direct bond, carbonyl or carbonyloxy; and V is phenyl substituted by 1-3 phenyl, alkoxy of 1-2 carbon atoms, or halogen, preferably bromine; R 2 is hydrogen or alkyl of 1-5 carbon atoms; R 3 is alkyl, substituted or unsubstituted cycloalkyl, straight-chain or branched alkyl of 1-5 carbon atoms substituted by aryl or substituted aryl, when R 1 is as above; or R 3 is aryl or substituted aryl group when R 1 is --OR 5 ', --NHSO 2 CH 3 , or --O--CH 2 --U--V and R 5 ' is aryl or a heterocyclic group and U and V are as above; R 4 is hydrogen or an ether or acyl residue; A is --CH 2 --CH 2 -- or cis--CH═CH--; B is --CH 2 --CH 2 -- or trans--CH═CH--; D is a direct bond, oxygen, or sulfur; Z is carbonyl or >CH OR 4 wherein OR 4 is in the α- or β-position; and X y is ##STR2## when Z is >CH OR 4 --, or ##STR3## or --CH═CH-- when Z is carbonyl; AND, WHEN R 1 is hydroxy, the physiologically compatible salts thereof with bases, have more prolonged activity than naturally-occurring prostaglandins.
Inventors
- 👤 Werner Skuballa
- 👤 Bernd Raduechel
- 👤 Helmut Vorbrueggen
- 👤 Walter Elger
- 👤 Olaf Loge
- 👤 Eckehard Schillinger
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 23:35
CPC Classifications
C; C07; C07D; C07D307/00; C07D307/77; C07D307/93; C07D307/935; C07C; C07C405/00
Claims Analysis
Total Claims: 83
Claim 1
Independent Claim
207 words
A (5Z, 13E) prostaglandin compound of the formula ##STR17## wherein R 1 is --OR 5 or --O--CH 2 --U--V, R 5 being a hydrogen atom, alkyl of 1-10 carbon atoms, phenyl, 1-naphthyl or 2-naphthyl, each of which can be substituted by up to 3 of halogen, phenyl, alkyl of 1-4 carbon atoms, chloromethyl, fluoromethyl, trifluoromethyl, carboxy, alkoxy and hydroxy or a heterocyclic ring of 5 or 6 ring members whose heteroatom is N, O or S, U being a direct bond, carbonyl or carbonyloxy, and V being phenyl substituted by one or more of phenyl, alkoxy of 1-2 carbon atoms, and halogen; R 2 is hydrogen or alkyl of 1-5 carbon atoms; R 3 is alkyl or cycloalkyl of up to 10 carbon atoms; A is cis-CH═CH--; p1 B is trans-CH═CH; D is a direct bond, oxygen, or sulfur; Z is carbonyl or >CH OR 4 wherein OR 4 is in the α- or β-position and R 4 is H, tetrahydropyranyl, tetrahydrofuranyl, α-ethoxyethyl, trimethylsilyl, and tri-p-xylysilyl, alkanoyl of up to 7 carbon atoms or benzoyl; and X y is ##STR18## when Z is >CH OR 4 --, or ##STR19## or --CH═CH--, when Z is carbonyl; and, when R 1 is hydroxy, physiologically acceptable salts thereof with bases.
Claim 2
Dependent Claim
207 words
A (5Z, 13E) prostaglandin compound of the formula ##STR17## wherein R 1 is --OR 5 or --O--CH 2 --U--V, R 5 being a hydrogen atom, alkyl of 1-10 carbon atoms, phenyl, 1-naphthyl or 2-naphthyl, each of which can be substituted by up to 3 of halogen, phenyl, alkyl of 1-4 carbon atoms, chloromethyl, fluoromethyl, trifluoromethyl, carboxy, alkoxy and hydroxy or a heterocyclic ring of 5 or 6 ring members whose heteroatom is N, O or S, U being a direct bond, carbonyl or carbonyloxy, and V being phenyl substituted by one or more of phenyl, alkoxy of 1-2 carbon atoms, and halogen; R 2 is hydrogen or alkyl of 1-5 carbon atoms; R 3 is alkyl or cycloalkyl of up to 10 carbon atoms; A is cis-CH═CH--; p1 B is trans-CH═CH; D is a direct bond, oxygen, or sulfur; Z is carbonyl or >CH OR 4 wherein OR 4 is in the α- or β-position and R 4 is H, tetrahydropyranyl, tetrahydrofuranyl, α-ethoxyethyl, trimethylsilyl, and tri-p-xylysilyl, alkanoyl of up to 7 carbon atoms or benzoyl; and X y is ##STR18## when Z is >CH OR 4 --, or ##STR19## or --CH═CH--, when Z is carbonyl; and, when R 1 is hydroxy, physiologically acceptable salts thereof with bases.
Claim 3
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-18,18-dimethyl-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 4
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 5
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 6
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-15,20-dimethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 7
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-15,20-dimethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 8
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-20-ethyl-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 9
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-20-ethyl-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 10
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-15-methyl-17-ethoxy-18,19,20-trinorprostadienl-16-inic acid, a compound of claim 1.
Claim 11
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-15-methyl-17-ethoxy-18,19,20-trinorprostadien-16-inic acid, a compound of claim 1.
Claim 12
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-15-methyl-17-cyclohexyl-18,19,20-trinorprostadien-16-inic acid, a compound of claim 1.
Claim 13
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-15-methyl-17-cyclohexyl-18,19,20-trinorprostadien-16-inic acid, a compound of claim 1.
Claim 14
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-18,18-dimethyl-15-methyl-20-norprostadien-16-inic acid, a compound of claim 1.
Claim 15
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-18,18-dimethyl-15-methyl-20-norprostadien-16-inic acid, a compound of claim 1.
Claim 16
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-prostadien-16-inic acid, a compound of claim 1.
Claim 17
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-prostadien-16-inic acid, a compound of claim 1.
Claim 18
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-20-ethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 19
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-20-ethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 20
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-20-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 21
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-20-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 22
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 23
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 24
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-17-cyclohexyl-18,19,20-trinor-prostadien-16inic acid, a compound of claim 1.
Claim 25
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-17-cyclohexyl-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 26
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-18,18-dimethyl-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 27
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-trihydroxy-18,18-dimethyl-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 28
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 29
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 30
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-20-ethyl-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 31
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-20-ethyl-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 32
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-15,20-dimethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 33
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-15,20-dimethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 34
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-15-methyl-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 35
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-15-methyl-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 36
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,15S)-9,11,15-Trihydroxy-15-methyl-17-cyclohexyl-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 37
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-15-methyl-17-cyclohexyl-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 38
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,15S)-9,11,15-Trihydroxy-18,18-dimethyl-15-methyl-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 39
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-18,18-dimethyl-15-methyl-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 40
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,14S)-9,11,15-Trihydroxy-prostadien-16-inic acid, a compound of claim 1.
Claim 41
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-prostadien-16-inic acid, a compound of claim 1.
Claim 42
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-20-ethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 43
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-20-ethyl-prostadien-16-inic acid, a compound of claim 1.
Claim 44
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-20-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 45
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-20-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 46
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 47
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 48
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-17-cyclohexyl-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 49
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-17-cyclohexyl-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 50
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-Trihydroxy-18,18-dimethyl-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 51
Dependent Claim
7 words
(5Z,13E)-(8R,9S,11R,12R,15R)-9,11,15-Trihydroxy-18,18-dimethyl-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 52
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15S)-11,15-Dihydroxy-15-methyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 53
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15R)-11,15-Dihydroxy-15-methyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 54
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15S)-11,15-Dihydroxy-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 55
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15R)-11,15-Dihydroxy-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 56
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,12R,15S)-9,15-dihydroxy-15-methyl-11-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 57
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,9S,12R,15R)-9,15-dihydroxy-15-methyl-11-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 58
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,11R,12R,15S)-11,15-dihydroxy-15-methyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 59
Dependent Claim
10 words
Methyl ester of (5Z,13E)-(8R,11R,12R,15R)-11,15-dihydroxy-15-methyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 60
Dependent Claim
10 words
Methyl ester of (5Z,10Z,13E)-(8R,12R,15S)-15-hydroxy-9-oxo-15-methyl-prostatrien-16-inic acid, a compound of claim 1.
Claim 61
Dependent Claim
10 words
Methyl ester of (5Z,10Z,13E)-(8R,12R,15R)-15-hydroxy-9-oxo-15-methyl-prostatrien-16-inic acid, a compound of claim 1.
Claim 62
Dependent Claim
10 words
Tris(hydroxymethyl)aminomethane salt of (5Z,13E)-(8R,9S,11R,12R,15S)-9,11,15-trihydroxy-15-methyl-prostadien-16-inic acid, a compound of claim 1.
Claim 63
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15S)-11,15-Dihydroxy-15-methyl-20-ethyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 64
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15R)-11,15-Dihydroxy-15-methyl-20-ethyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 65
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15S)-11,15)-11,15-Dihydroxy-15,20-dimethyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 66
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15R)-11,15-Dihydroxy-15,20-dimethyl-9-oxo-prostadien-16-inic acid, a compound of claim 1.
Claim 67
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15S)-11,15-Dihydroxy-15-methyl-9-oxo-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 68
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15R)-11,15-Dihydroxy-15-methyl-9-oxo-17-ethoxy-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 69
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15S)-11,15-Dihydroxy-18,18-dimethyl-15-methyl-9-oxo-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 70
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15R)-11,15-Dihydroxy-18,18-dimethyl-15-methyl-9-oxo-20-nor-prostadien-16-inic acid, a compound of claim 1.
Claim 71
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15S)-11,15-Dihydroxy-15-methyl-17-cyclohexyl-9-oxo-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 72
Dependent Claim
7 words
(5Z,13E)-(8R,11R,12R,15R)-11,15-Dihydroxy-15-methyl-17-cyclohexyl-9-oxo-18,19,20-trinor-prostadien-16-inic acid, a compound of claim 1.
Claim 73
Dependent Claim
12 words
A compound of claim 1, in the form of a free acid.
Claim 74
Dependent Claim
12 words
A compound of claim 1, in the form of a methyl ester.
Claim 75
Dependent Claim
11 words
A compound of claim 1, wherein D is a direct bond.
Claim 76
Dependent Claim
9 words
A compound of claim 1, wherein D is oxygen.
Claim 77
Dependent Claim
16 words
A compound of claim 1, wherein D is a direct bond and R 3 is cycloalkyl.
Claim 78
Dependent Claim
9 words
A compound of claim 1, wherein Z is carbonyl.
Claim 79
Dependent Claim
9 words
A compound of claim 1, wherein Z is ##STR20##
Claim 80
Dependent Claim
10 words
A compound of claim 1, wherein X Y is ##STR21##
Claim 81
Dependent Claim
10 words
A compound of claim 1, wherein X Y is ##STR22##
Claim 82
Dependent Claim
10 words
A compound of claim 1, wherein X Y is --CH═CH--.
Claim 83
Dependent Claim
34 words
A leuteolytic pharmaceutical composition comprising an amount per unit dosage effective to induce menstruation or interrupt pregnancy in a female mammal of a compound of claim 1, in admixture with a pharmaceutically acceptable carrier.
References Cited (Backward Citations)
JPS50140427A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-02-13 | 1981-08-15 | 1982-02-14 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-02-13 | 1985-08-15 | 1986-02-14 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-02-13 | 1989-08-15 | 1990-02-14 | $7700.00 | Window Closed / Lapsed |