US4608388A
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Novel [4,2,0]bicyclooctane derivatives with valuable therapeutic properties
Assignee: Syntex USA LLC
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Filing: 1985-03-27
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Granted: 1986-08-26
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Expires: 2005-03-27
Abstract
Abstract Compounds useful in treating cardiovascular disorders such as thrombosis, hypertension, and atherosclerosis are compounds depicted in formulas (1), (2), and (3): ##STR1## wherein: n is 2 or 3; R 1 is CH 2 OH, CHO, CO 2 R or CO 2 H; R 2 is hydrogen or methyl; and R 3 is linear or branched alkyl having 5-10 carbon atoms, ##STR2## optionally substituted with lower alkyl, lower alkoxy, trifluoromethyl, or halogen, in which a is 0, 1 or 2; b is 3-7; m is 1 or 2; and R is ##STR3## in which each R 4 is independently hydrogen or lower alkyl having 1-6 carbon atoms, and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Inventors
- 👤 Arthur F. Kluge
- 👤 Anthony L. Willis
- 👤 Counde O'Yang
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 19:25
CPC Classifications
H; H04; H04N; H04N9/00; H04N9/79; H04N9/7921; A; A61; A61P; A61P3/00; A61P3/06; A61P7/00; A61P7/02; A61P9/00; A61P9/10; A61P9/12; C; C07; C07C; C07C35/00; C07C35/22; C07C35/23; C07C35/31; C07C403/00; C07C403/06; C07C403/08; C07C403/14; C07C403/16; C07C403/20; C07C45/00; C07C45/27; C07C45/29; C07C45/292; C07C45/30; C07C45/305; C07C47/00; C07C47/20; C07C47/26; C07C47/267; C07C47/27; C07C47/273; C07C47/277; C07C49/00; C07C49/587; C07C49/703; C07C49/743; C07C49/747; C07C59/00; C07C59/40; C07C59/42; C07C59/46; C07C59/56; C07F; C07F7/00; C07F7/02; C07F7/08; C07F7/18; C07F7/1804; C07B; C07B2200/00; C07B2200/07; C07B2200/09; C07C2601/00; C07C2601/12; C07C2601/14
Claims Analysis
Total Claims: 56
Claim 1
Independent Claim
102 words
A compound of formula (1), (2) or (3) ##STR23## wherein: n is 2 or 3; R 1 is CH 2 OH, CHO, CO 2 R or CO 2 H; R 2 is hydrogen or methyl; and R 3 is linear or branched alkyl having 5-10 carbon atoms, ##STR24## optionally substituted with lower alkyl, lower alkoxy, trifluoromethyl, or halogen, in which a is 0, 1 or 2; b is 3-7; m is 1 or 2; and R is ##STR25## in which each R 4 is independently hydrogen or lower alkyl having 1-6 carbon atoms, and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Claim 2
Dependent Claim
102 words
A compound of formula (1), (2) or (3) ##STR23## wherein: n is 2 or 3; R 1 is CH 2 OH, CHO, CO 2 R or CO 2 H; R 2 is hydrogen or methyl; and R 3 is linear or branched alkyl having 5-10 carbon atoms, ##STR24## optionally substituted with lower alkyl, lower alkoxy, trifluoromethyl, or halogen, in which a is 0, 1 or 2; b is 3-7; m is 1 or 2; and R is ##STR25## in which each R 4 is independently hydrogen or lower alkyl having 1-6 carbon atoms, and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Claim 3
Dependent Claim
51 words
A compound of claim 1 wherein n is 2 or 3, R 1 is CO 2 H, CO 2 R or CHO; R 2 is hydrogen or methyl; and R 3 is linear or branched alkyl of 5 to 10 carbons, ##STR26## and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Claim 4
Dependent Claim
52 words
A compound of claim 2 wherein n is 2 or 3, R 1 is CHO, CO 3 R or CO 2 H, R 2 is hydrogen or methyl, and R 3 is linear or branched alkyl of 5 or 7 carbon atoms, ##STR27## and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Claim 5
Dependent Claim
41 words
A compound of claim 3 wherein n is 2 or 3, R 1 is CO 2 R or CO 2 H, R 2 is hydrogen or methyl, and R 3 is n-pentyl, and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Claim 6
Dependent Claim
41 words
A compound of claim 3 wherein n is 2 or 3, R 1 is CO 2 R or CO 2 H, R 2 is hydrogen or methyl, and R 3 is ##STR28## and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 7
Dependent Claim
33 words
A compound of claim 5 wherein n is 2, R 1 is CO 2 H, R 2 is hydrogen, and R 3 is ##STR29## and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Claim 8
Dependent Claim
20 words
A compound of claim 6 wherein a is 0 or 1, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 9
Dependent Claim
22 words
A compound of claim 7 wherein a is 0 and b is 5, and the pharmaceutically acceptable, non-toxic, salts and esters thereof.
Claim 10
Dependent Claim
15 words
A compound of claim 5 wherein n is 3 and a is 0 or 1.
Claim 11
Dependent Claim
26 words
A compound of claim 7 in which a is 0 and b is 5, namely (Z)-(3'S,1S,2S,3R,6S)-4-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylidene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 12
Dependent Claim
21 words
The racemic modification of the compound of claim 10, namely (Z)-(3S*,1S*,2S*,3R*,6S*)-4-[2-(3'-hydroxy-4'-cyclohexyprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylidene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 13
Dependent Claim
20 words
The (E)-isomer of the compound of claim 10, namely (E)-(3'S,1S,2S,3R,6S)-4-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 14
Dependent Claim
20 words
The (E)-isomer of the compound of claim 11, namely (E)-(3'S*,1S*,2S*,3R*,6S*)-4-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 15
Dependent Claim
24 words
A compound of claim 7 in which a is 0 and b is 4, namely (Z)-(3'S,1S,2S,3R,6S)-4-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylidene]butyric acid, and the pharmaceutically acceptable non-toxic salts thereof.
Claim 16
Dependent Claim
21 words
The racemic modification of the compound of claim 14, namely (Z)-(3'S*,1S*,2S*,3R*,6S*)-4-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 17
Dependent Claim
20 words
The (E)-isomer of the compound of claim 14, namely (E)-(3'S,1S,2S,3R,6S)-4-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 18
Dependent Claim
20 words
The (E)-isomer of the compound of claim 15, namely (E)-(3'S*,1S*,2S*,3R*,6S*)-4-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 19
Dependent Claim
25 words
A compound of claim 9 wherein a is 0 and b is 4, namely (Z)-(3'S,1S,3R,6S)-5-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 20
Dependent Claim
21 words
The racemic modification of the compound of claim 18, namely (Z)-(3'S*,1S*,2S*,3R*,6S*)-5-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 21
Dependent Claim
21 words
The (E)-isomer of the compound of claim 19, namely (E)-(3'S,1S,2S,3R,6S)-5-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0 -oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 22
Dependent Claim
20 words
The (E)-isomer of the compound of claim 19, namely (E)-(3'S*,1S*,2S*,3R*,6S*)-5-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 23
Dependent Claim
26 words
A compound of claim 9 in which a is 0 and b is 5, namely (Z)-(3'S,1S,2S,3R,6S)-5-[2-(3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 24
Dependent Claim
21 words
The racemic modification of the compound of claim 22, namely (Z)-(3'S*,1S*,2S*,3R*,6S*)-5-[2-(3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 25
Dependent Claim
20 words
The (E)-isomer of the compound of claim 22, namely (E)-(3'S,1S,2S,3R,6S)-5-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 26
Dependent Claim
22 words
The (E)-isomer of the compound of claim 23, namely (E)-(3'S*,1S*,2S*, 3R*, 6S*)-5-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 27
Dependent Claim
26 words
A compound of claim 9 in which a is 0 and b is 4, namely (Z)-(3'S,1R,2R,3S,6R)-5-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 28
Dependent Claim
21 words
The racemic modification of the compound of claim 26, namely (Z)-(3'S*,1R*,2R*,3S*,6R*)-5-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 29
Dependent Claim
26 words
A compound of claim 7 in which a is 0 and b is 4, namely (Z)-(3'S,1R,2R,3S,6R)-4-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 30
Dependent Claim
21 words
The racemic modification of the compound of claim 28, namely (Z)-(3'S*,1R*,2R*,3S*,6R*)-4-[2-(3'-hydroxy-3'-cyclopentylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 31
Dependent Claim
26 words
A compound of claim 7 in which a is 0 and b is 5, namely (Z)-(3'S,1R,2R,3S,6R)-4-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 32
Dependent Claim
21 words
The racemic modification of the compound of claim 30, namely (Z)-(3'S*,1R*,2R*,3S*,6R*)-4-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 33
Dependent Claim
26 words
A compound of claim 9 in which a is 0 and b is 5, namely (Z)-(3'S,1R,2R,3S,6R)-5-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.3.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 34
Dependent Claim
21 words
The racemic modification of the compound of claim 32, namely (Z)-(3'S*,1R*,2R*,3S*,6R*)-5-[2-(3'-hydroxy-3'-cyclohexylprop-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]pentanoic acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 35
Dependent Claim
37 words
A compound of claim 3 wherein n is 2, R 1 is CO 2 H, R 2 is hydrogen, and R 3 is --(CH 2 ) m -phenyl, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 36
Dependent Claim
22 words
A compound of claim 34 in which m is 1, namely (Z)-(3'S,1S,2S,3R,6S)-4-[2-(3'-hydroxy-4'-phenylbut-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 37
Dependent Claim
21 words
The racemic modification of the compound of claim 35, namely (Z)-(3'S*,1S*,2S*,3R*,6S*)-4-[2-(3'-hydroxy-4'-phenylbut-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 38
Dependent Claim
20 words
The (E)-isomer of the compound of claim 35, namely (E)-(3'S,1S,2S,3R,6S)-4-[2-(3'-hydroxy-4'-phenylbut-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 39
Dependent Claim
21 words
The racemic modification of the compound of claim 37, namely (E)-(3'S*,1R*,2R*,3S*,6R*)-4-[2-(3'-hydroxy-4'-phenylbut-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 40
Dependent Claim
22 words
A compound of claim 34 in which m is 1, namely (Z)-(3'S,1R,2R,3S,6R)-4-[2-(3'-hydroxy-4'-phenylbut-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 41
Dependent Claim
21 words
The racemic modification of the compound of claim 39, namely (Z)-(3'S*,1R*,2R*,3S*,6R*)-4-[2-(3'-hydroxy-4'-phenylbut-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 42
Dependent Claim
31 words
A compound of claim 3 wherein n is 2, R 1 is CO 2 H, R 2 is hydrogen, and R 3 is linear or branched alkyl of 5 carbon atoms.
Claim 43
Dependent Claim
19 words
A compound of claim 41 which is named (Z)-(3'S,1S,2S,3R,6S)-4-[2-(3'-hydroxyoct-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 44
Dependent Claim
21 words
The racemic modification of the compound of claim 42, namely (Z)-(3'S*,1S*,2S*,3R*,6S*)-4-[2-(3'-hydroxyoct-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 45
Dependent Claim
19 words
A compound of claim 41 which is named (Z)-(3'S,1R,2R,3S,6R)-4-[2-(3'-hydroxyoct-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 46
Dependent Claim
21 words
The racemic modification of the compound of claim 44, namely (Z)-(3'S*,1R*,2R*,3S*,6R*)-4-[2-(3'-hydroxyoct-1'-ynyl)-3-hydroxybicyclo[4.2.0]-oct-7-ylildene]butyric acid, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 47
Dependent Claim
38 words
A method for treating cardiovascular disorders in mammals which comprises administering a therapeutically effective amount of a compound of claim 1, or a pharmaceuticlaly acceptable non-toxic salt or ester thereof, to a subject in need of such treatment.
Claim 48
Dependent Claim
10 words
The method of claim 46 wherein the disorder is atherosclerosis.
Claim 49
Dependent Claim
12 words
The method of claim 46 wherein the disorder involves a thrombotic condition.
Claim 50
Dependent Claim
12 words
The method of claim 46 wherein the disorder involves a vasospastic condition.
Claim 51
Dependent Claim
10 words
The method of claim 46 wherein the disorder is hypertension.
Claim 52
Dependent Claim
12 words
The method of claim 46 wherein the disorder is elevated cholesterol levels.
Claim 53
Dependent Claim
25 words
A pharmaceutical composition containing at least one suitable pharmaceutical excipient and a compound of claim 1 or a pharmaceutically acceptable, non-toxic salt or ester thereof.
Claim 54
Dependent Claim
19 words
A compound of claim 1 in which n is 2, and the pharmaceutically acceptable non-toxic salts and esters thereof.
Claim 55
Dependent Claim
20 words
A compound of claim 1 in which R 2 is hydrogen, and the pharmaceutically acceptable, non-toxic salts and esters thereof.
Claim 56
Dependent Claim
22 words
A compound of claim 1 in which R 3 is ##STR30## in which a is 0 or 1 and b is 3-7.
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) | 1989-08-25 | 1990-02-24 | 1990-08-26 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-08-25 | 1994-02-24 | 1994-08-26 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-08-25 | 1998-02-24 | 1998-08-26 | $7700.00 | Window Closed / Lapsed |