US4444784A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Antihypercholesterolemic compounds
Assignee: Merck Capital Resources Inc
•
Filing: 1980-12-18
•
Granted: 1984-04-24
•
Expires: 2000-12-18
Abstract
Abstract 6(R)-[2-(8'-acyloxy-2'-methyl-6'-methyl (or hydrogen)-polyhydronaphthyl-1')-ethyl]-4 (R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-ones are prepared by acylation of the corresponding 8'-hydroxy compounds. The products are strong inhibitors of the biosynthesis of cholesterol.
Inventors
- 👤 William F. Hoffman
- 👤 Robert L. Smith
- 👤 Alvin K. Willard
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 12:54
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30
Claims Analysis
Total Claims: 24
Claim 1
Independent Claim
128 words
A compound of the formula: ##STR68## wherein R' is H or CH 3 ; R is (1) 1,1-dimethylpropyl, (2) C 3-10 cycloalkyl, (3) C 2-10 alkenyl, (4) C 1-10 CF 3 -substituted alkyl, (5) phenyl, (6) halophenyl, (7) phenyl-C 1-3 alkyl, (8) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR69## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 2
Dependent Claim
128 words
A compound of the formula: ##STR68## wherein R' is H or CH 3 ; R is (1) 1,1-dimethylpropyl, (2) C 3-10 cycloalkyl, (3) C 2-10 alkenyl, (4) C 1-10 CF 3 -substituted alkyl, (5) phenyl, (6) halophenyl, (7) phenyl-C 1-3 alkyl, (8) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR69## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 3
Dependent Claim
11 words
The compound of claim 1 wherein R' is CH 3 .
Claim 4
Dependent Claim
9 words
The compound of claim 1 wherein R is 1,1-dimethylpropyl.
Claim 5
Dependent Claim
9 words
The compound of claim 2 wherein R is 1,1-dimethylpropyl.
Claim 6
Dependent Claim
16 words
The compound of claim 1 wherein none of X, Y or Z is a double bond.
Claim 7
Dependent Claim
143 words
A pharmaceutical antihypercholesterolemic composition comprising a pharmaceutical carrier and an antihypercholesterolemic effective amount of a compound of structural formula: ##STR70## in which R' is H or CH 3 ; R is (1) 1,1-dimethylpropyl, (2) C 3-10 cycloalkyl, (3) C 2-10 alkenyl, (4) C 1-10 CF 3 -substituted alkyl, (5) phenyl, (6) halophenyl, (7) phenyl-C 1-3 alkyl, (8) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR71## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 8
Dependent Claim
143 words
A pharmaceutical antihypercholesterolemic composition comprising a pharmaceutical carrier and an antihypercholesterolemic effective amount of a compound of structural formula: ##STR70## in which R' is H or CH 3 ; R is (1) 1,1-dimethylpropyl, (2) C 3-10 cycloalkyl, (3) C 2-10 alkenyl, (4) C 1-10 CF 3 -substituted alkyl, (5) phenyl, (6) halophenyl, (7) phenyl-C 1-3 alkyl, (8) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR71## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 9
Dependent Claim
11 words
The composition of claim 6 wherein R' is CH 3 .
Claim 10
Dependent Claim
9 words
The composition of claim 6 wherein R is 1,1-dimethylpropyl.
Claim 11
Dependent Claim
9 words
The composition of claim 7 wherein R is 1,1-dimethylpropyl.
Claim 12
Dependent Claim
16 words
The composition of claim 6 wherein none of X, Y or Z is a double bond.
Claim 13
Independent Claim
151 words
A method of treating hypercholesterolemia in a patient in need of such treatment which comprises administration of an antihypercholesterolemic effective amount of a compound of structural formula: ##STR72## in which R' is H or CH 3 ; R is (1) 1,1-dimethylpropyl, (2) C 3-10 cycloalkyl, (3) C 2-10 alkenyl, (4) C 1-10 CF 3 -substituted alkyl, (5) phenyl, (6) halophenyl, (7) phenyl-C 1-3 alkyl, (8) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR73## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 14
Independent Claim
151 words
A method of treating hypercholesterolemia in a patient in need of such treatment which comprises administration of an antihypercholesterolemic effective amount of a compound of structural formula: ##STR72## in which R' is H or CH 3 ; R is (1) 1,1-dimethylpropyl, (2) C 3-10 cycloalkyl, (3) C 2-10 alkenyl, (4) C 1-10 CF 3 -substituted alkyl, (5) phenyl, (6) halophenyl, (7) phenyl-C 1-3 alkyl, (8) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR73## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 15
Dependent Claim
11 words
The method of claim 11 wherein R' is CH 3 .
Claim 16
Dependent Claim
9 words
The method of claim 11 wherein R is 1,1-dimethylpropyl.
Claim 17
Dependent Claim
9 words
The method of claim 12 wherein R is 1,1-dimethylpropyl.
Claim 18
Dependent Claim
16 words
The method of claim 11 wherein none of X, Y or Z is a double bond.
Claim 19
Dependent Claim
126 words
A compound of the formula: ##STR74## wherein R' is H or CH 3 ; R is (1) C 3-10 cycloalkyl, (2) C 2-10 alkenyl, (3) C 1-10 CF 3 -substituted alkyl, (4) phenyl, (5) halophenyl, (6) phenyl-C 1-3 alkyl (7) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone or the corresponding dihydroxy acid of the formula: ##STR75## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 20
Dependent Claim
126 words
A compound of the formula: ##STR74## wherein R' is H or CH 3 ; R is (1) C 3-10 cycloalkyl, (2) C 2-10 alkenyl, (3) C 1-10 CF 3 -substituted alkyl, (4) phenyl, (5) halophenyl, (6) phenyl-C 1-3 alkyl (7) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone or the corresponding dihydroxy acid of the formula: ##STR75## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 21
Dependent Claim
141 words
A pharmaceutical antihypercholesterolemic composition comprising a pharmaceutical carrier and an antihypercholesterolemic effective amount of a compound of structural formula: ##STR76## in which R' is H or CH 3 ; R is (1) C 3-10 cycloalkyl, (2) C 2-10 alkenyl, (3) C 1-10 CF 3 -substituted alkyl, (4) phenyl, (5) halophenyl, (6) phenyl-C 1-3 alkyl, (7) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR77## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 22
Dependent Claim
141 words
A pharmaceutical antihypercholesterolemic composition comprising a pharmaceutical carrier and an antihypercholesterolemic effective amount of a compound of structural formula: ##STR76## in which R' is H or CH 3 ; R is (1) C 3-10 cycloalkyl, (2) C 2-10 alkenyl, (3) C 1-10 CF 3 -substituted alkyl, (4) phenyl, (5) halophenyl, (6) phenyl-C 1-3 alkyl, (7) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR77## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted-C 1-4 alkyl ester of said acid.
Claim 23
Independent Claim
150 words
A method of treating hypercholesterolemia in a patient in need of such treatment which comprises administration of an antihypercholesterolemic effective amount of a compound of structural formula: ##STR78## in which R' is H or CH 3 ; R is (1) C 3-10 cycloalkyl, (2) C 2-10 alkenyl, (3) C 1-10 CF 3 -substituted alkyl, (4) phenyl, (5) halophenyl, (6) phenyl-C 1-3 alkyl, (7) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR79## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted C 1-4 alkyl ester of said acid.
Claim 24
Independent Claim
150 words
A method of treating hypercholesterolemia in a patient in need of such treatment which comprises administration of an antihypercholesterolemic effective amount of a compound of structural formula: ##STR78## in which R' is H or CH 3 ; R is (1) C 3-10 cycloalkyl, (2) C 2-10 alkenyl, (3) C 1-10 CF 3 -substituted alkyl, (4) phenyl, (5) halophenyl, (6) phenyl-C 1-3 alkyl, (7) substituted phenyl-C 1-3 alkyl in which the substituent is halo, C 1-3 alkyl or C 1-3 alkoxy; the dotted lines at X, Y and Z represent possible double bonds, said double bonds, when any are present, being either X and Z in combination or X, Y or Z alone; or the corresponding dihydroxy acid of the formula: ##STR79## or a pharmaceutically acceptable salt of said acid, a C 1-4 alkyl ester of said acid or a phenyl-, dimethylamino-, or acetylamino-substituted C 1-4 alkyl ester of said acid.
References Cited (Backward Citations)
US3072709A
Cited
US3344169A
Cited
US3983140A
Cited
US4049495A
Cited
US4137322A
Cited
JPS559024A
Cited
US4323648A
Cited
US4319039A
Cited
US4231938A
Cited
US4294846A
Cited
US4342767A
Cited
US4293496A
Cited
US4282155A
Cited
US4351844A
Cited
US4346227A
Cited
US4343814A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-04-24 | 1987-10-24 | 1988-04-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-04-24 | 1991-10-24 | 1992-04-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-04-24 | 1995-10-24 | 1996-04-24 | $7700.00 | Window Closed / Lapsed |