US5393776A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Tocotrienol analogs in the treatment of hypercholesterolemia and hyperlipidemia
Assignee: Bristol Myers Squibb Co
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Filing: 1994-05-13
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Granted: 1995-02-28
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Expires: 2014-05-13
Abstract
Abstract This invention relates to structurally novel acyclic tocotrienol analogs, which are useful for cholesterol/lipid lowering in cases of hypercholesterolemia and hyperlipidemia, and for atherosclerosis. Also provided are pharmaceutical compositions and a method of use employing those compositions.
Inventors
- 👤 Bradley C. Pearce
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 15:27
CPC Classifications
C; C07; C07F; C07F5/00; C07F5/02; C07F5/025; C07C; C07C215/00; C07C215/74; C07C215/76; C07C217/00; C07C217/78; C07C217/80; C07C217/82; C07C217/84; C07C235/00; C07C235/42; C07C235/44; C07C235/46; C07C271/00; C07C271/06; C07C271/08; C07C271/26; C07C271/28; C07C271/40; C07C271/42; C07C271/44; C07C311/00; C07C311/01; C07C311/02; C07C311/03; C07C311/08; C07C311/22; C07C311/29; C07C317/00; C07C317/16; C07C317/22; C07C323/00; C07C323/10; C07C323/18; C07C323/20; C07C33/00; C07C33/02; C07C39/00; C07C39/18; C07C39/19; C07C43/00; C07C43/02; C07C43/20; C07C43/215; C07C43/23; C07C45/00; C07C45/56; C07C45/567; C07C45/61; C07C45/67; C07C45/68; C07C45/70; C07C45/71; C07C49/00; C07C49/76; C07C49/82; C07C49/835; C07C49/84; C07D; C07D339/00; C07D339/08
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
179 words
A method of treating hypercholesterolemia and hyperlipidemia which comprises administering to a patient in need of such treatment an effective amount of a method of the formula (II) ##STR41## wherein R 1 , R 2 , R 3 and R 4 represent hydrogen, C 1 -C 5 lower alkyl, halogen, COCH 3 , CH 2 OH,CH 2 CH 2 OH, OH or OMe; R 5 represents hydrogen or methyl; Y represents hydrogen or a hydrogen bond donating group, selected from the group consisting of NHSO 2 Me, NHCO 2 Me, NH 2 , CH 2 OH, B(OH) 2 , CONH 2 , SO 2 NH 2 , or OH, with the proviso that Y is not hydrogen when R 1 , R 2 , R 3 and R 4 are all hydrogen; X represents oxygen, sulfur, NH, N (C 1 -C 5 lower alkyl), N(acyl), CH 2 , CO, SO, SO 2 ; n 1 is 1 or 2; and n 2 is 1 or 2; or nontoxic pharmaceutically acceptable acid addition salts, hydrate, solvate or metal salts thereof.
Claim 2
Independent Claim
179 words
A method of treating hypercholesterolemia and hyperlipidemia which comprises administering to a patient in need of such treatment an effective amount of a method of the formula (II) ##STR41## wherein R 1 , R 2 , R 3 and R 4 represent hydrogen, C 1 -C 5 lower alkyl, halogen, COCH 3 , CH 2 OH,CH 2 CH 2 OH, OH or OMe; R 5 represents hydrogen or methyl; Y represents hydrogen or a hydrogen bond donating group, selected from the group consisting of NHSO 2 Me, NHCO 2 Me, NH 2 , CH 2 OH, B(OH) 2 , CONH 2 , SO 2 NH 2 , or OH, with the proviso that Y is not hydrogen when R 1 , R 2 , R 3 and R 4 are all hydrogen; X represents oxygen, sulfur, NH, N (C 1 -C 5 lower alkyl), N(acyl), CH 2 , CO, SO, SO 2 ; n 1 is 1 or 2; and n 2 is 1 or 2; or nontoxic pharmaceutically acceptable acid addition salts, hydrate, solvate or metal salts thereof.
Claim 3
Dependent Claim
22 words
The method of claim 1 wherein the olefin unit in the polyprenyl side chain is all cis, all trans, or a cis/trans-mixture.
Claim 4
Dependent Claim
13 words
The method of claim 1 wherein the compound is 2,3-dimethyl-4-[5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]phenol.
Claim 5
Dependent Claim
12 words
The method of claim 1 wherein the compound is 4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)oxy]phenol.
Claim 6
Dependent Claim
12 words
The method of claim 1 wherein the compound is 4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)thio]phenol.
Claim 7
Dependent Claim
13 words
The method of claim 1 wherein the compound is 2,3,5,6-tetrafluoro-4-[(5,9,13-trimethyl-4-(E), 8(E), 12-tetradecatrienyl) oxy]phenol.
Claim 8
Dependent Claim
13 words
The method of claim 1 wherein the compound is 1-[5-hydroxy-2-(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyloxy) phenyl]ethanone.
Claim 9
Dependent Claim
12 words
The method of claim 1 wherein the compound is 4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)oxy]aniline.
Claim 10
Dependent Claim
13 words
The method of claim 1 wherein the compound is N-[4-(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)oxy]phenyl] methanesulfonamide.
Claim 11
Dependent Claim
13 words
The method of claim 1 wherein the compound is 4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]benzenemethanol.
Claim 12
Dependent Claim
13 words
The method of claim 1 wherein the compound is 3,5-dimethyl-4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]phenol.
Claim 13
Dependent Claim
12 words
The method of claim 1 wherein the compound is 2-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)oxy]phenol.
Claim 14
Dependent Claim
13 words
The method of claim 1 wherein the compound is 3-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]benzenemethanol.
Claim 15
Dependent Claim
12 words
The method of claim 1 wherein the compound is 3-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)oxy]phenol.
Claim 16
Dependent Claim
13 words
The method of claim 1 wherein the compound is 4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)amino] phenol.
Claim 17
Dependent Claim
13 words
The method of claim 1 wherein the compound is 2,3-dimethyl-4-[(4,8,12-3(E), 7(E), 11-tridecatrienyl)oxy] phenol.
Claim 18
Dependent Claim
13 words
The method of claim 1 wherein the compound is 3,5-dimethyl-4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]aniline.
Claim 19
Dependent Claim
14 words
The method of claim 1 wherein the compound is N-[[3,5-dimethyl-4-[(5,9,13-trimethyl-4(e), 8(E), 12-tetradecatrienyl) oxy]]phenyl]methyl carbamate.
Claim 20
Dependent Claim
13 words
The method of claim 1 wherein the compound is 2,3,5-trimethyl-4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]phenol.
Claim 21
Dependent Claim
12 words
The method of claim 1 wherein the compound is 4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)oxy]benzamide.
Claim 22
Dependent Claim
13 words
The method of claim 1 wherein the compound is 4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl)oxy] benzenesulfonamide.
Claim 23
Dependent Claim
14 words
The method of claim 1 wherein the compound is 2-hydroxy-4,6-dimethyl-5-[(5,9,13-trimethyl-4(E), 8 (E), 12-tetradecatrienyl)oxy]-1,3 -benzenedimethanol.
Claim 24
Dependent Claim
12 words
The method of claim 1 wherein the compound is 1-(4-hydroxyphenyl)-6,10,14-trimethyl-5(E), 9(E), 13-pentadecatrien-1-one.
Claim 25
Dependent Claim
14 words
The method of claim 1 wherein the compound is 2-hydroxy-5-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]benzene ethanol.
Claim 26
Dependent Claim
10 words
The method of claim 1 wherein the compound is 3,5-dimethyl-4-[(5,9,13-trimethyl-4,8,12-tetradecatrienyl)oxy]phenol.
Claim 27
Dependent Claim
13 words
The method of claim 1 wherein the compound is 3,5-dimethoxy-4-[(5,9,13-trimethyl-4(E), 8(E), 12-tetradecatrienyl) oxy]phenol.
Claim 28
Dependent Claim
13 words
The method of claim 1 wherein the compound is 4-[(1,1,5,9,13-pentamethyl-4(E), 8(E), 12-tetradecatrienyl)oxy]phenol hydrate.
Claim 29
Dependent Claim
24 words
The method of treating hypercholesterolemia according to claim 1 which comprises administering to said patient an effective amount of a compound of formula (II).
Claim 30
Dependent Claim
24 words
The method of treating hyperlipidemia according to claim 1 which comprises administering to said patient an effective amount of a compound of formula (II).
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) | 1998-02-27 | 1998-08-29 | 1999-02-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-02-27 | 2002-08-29 | 2003-02-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-02-27 | 2006-08-29 | 2007-02-28 | $7700.00 | Window Closed / Lapsed |