EP0259087A2
Expired / Lapsed
EP
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Prodrugs of antihypercholesterolemic compounds
Assignee: Merck and Co Inc
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Filing: 1987-08-25
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Granted: —
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Expires: 2007-08-25
Abstract
Abstract Prodrugs of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors which are useful as antihypercholesterolemic agents and are represented by the following general structural formula (I): are disclosed.
Inventors
- 👤 Wasyl Halczenko
- 👤 George Hartman
- 👤 Steven Pitzenberger
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 05:07
CPC Classifications
C; C07; C07H; C07H15/00; C07H15/26; A; A61; A61P; A61P3/00; A61P3/06; C07D; C07D319/00; C07D319/04; C07D319/06
Claims Analysis
Total Claims: 11
Claim 1
Independent Claim
224 words
A compound represented by the general structural formula (I): wherein: R is selected from a group consisting of: (a) wherein n is 1 to 5; R 1 is hydrogen or methyl; A is or R 2 - C H, in which R 2 is hydrogen or hydroxyl; B is - C HR3, in which R 3 is hydrogen or hydroxyl; a, b, c and d represent single bonds, one of a, b, c and d represent a double bond or both a and c or both b and d represents double bonds, provided that when a is a double bond, A is or C H = and when d is a double bond, B is = C H; or (b) wherein: E is -CH 2 -, -CH 2 CH 2 -or -CH=CH-; R 4 and R 5 are independently C 1-3 alkyl, fluoro, bromo or chloro; and R 6 is phenyl, benzyloxy, substituted phenyl or substituted benzyloxy in which the phenyl group in each case is substituted with one or more substituents selected from C l . 3 alkyl, fluoro, bromo or chloro; R 7 is hydrogen or C 1-6 alkyl; R 8 is C 1-6 alkyl; and R 9 is C 1-6 alkyl, C 1-6 acyloxy-C 1-6 alkyl, C 1-6 alkoxyacyloxy-C 1-6 alkyl or a group selected from (1) (5-(1,1-dimethylethyl)-2-oxo-1,3-dioxol-4-yl)methyl; or (2) 2-(β-D-galactosidyl)ethyl.
Claim 2
Dependent Claim
224 words
A compound represented by the general structural formula (I): wherein: R is selected from a group consisting of: (a) wherein n is 1 to 5; R 1 is hydrogen or methyl; A is or R 2 - C H, in which R 2 is hydrogen or hydroxyl; B is - C HR3, in which R 3 is hydrogen or hydroxyl; a, b, c and d represent single bonds, one of a, b, c and d represent a double bond or both a and c or both b and d represents double bonds, provided that when a is a double bond, A is or C H = and when d is a double bond, B is = C H; or (b) wherein: E is -CH 2 -, -CH 2 CH 2 -or -CH=CH-; R 4 and R 5 are independently C 1-3 alkyl, fluoro, bromo or chloro; and R 6 is phenyl, benzyloxy, substituted phenyl or substituted benzyloxy in which the phenyl group in each case is substituted with one or more substituents selected from C l . 3 alkyl, fluoro, bromo or chloro; R 7 is hydrogen or C 1-6 alkyl; R 8 is C 1-6 alkyl; and R 9 is C 1-6 alkyl, C 1-6 acyloxy-C 1-6 alkyl, C 1-6 alkoxyacyloxy-C 1-6 alkyl or a group selected from (1) (5-(1,1-dimethylethyl)-2-oxo-1,3-dioxol-4-yl)methyl; or (2) 2-(β-D-galactosidyl)ethyl.
Claim 3
Dependent Claim
11 words
A compound of Claim 1 wherein R is the group (b).
Claim 4
Dependent Claim
11 words
A compound of Claim 2 wherein E is -CH = CH-.
Claim 5
Dependent Claim
23 words
A compound of Claim 3 wherein: R 4 and R 5 independently are C 1-3 alkyl; and R 6 is a substituted phenyl.
Claim 6
Dependent Claim
8 words
A compound of Claim 4 wherein R is:
Claim 7
Dependent Claim
23 words
A compound of Claim 5 wherein R 9 is C 1-6 alkyl, C 1-6 acyloxy-C 1-6 alkyl, or C 1-6 alkoxyacyloxy-C 1-6 alkyl.
Claim 8
Dependent Claim
21 words
A compound of Claim 6 which is (1) ethyl 6(S)-E-[2-[(4'-fluoro-3,3',5-trimethyl)-[1,1'-biphenyl]-2-yl]ethenyl]-2,2-dimethyl-1,3-dioxane-4-(R)-acetate; (2) (2,2-dimethyl-1-oxopropoxy)methyl 8-(S)-E-[2-[(4'-fluoro-3,3',5-trimethyl)[1,1'-biphenyl] -2-yl]-ethenyl]-2,2-dimethyl-1,3-dioxane-4(R)-acetate; (3) [5-(1,1-dimethylethyl)-2-oxo-1,3-dioxo)-4-yl]-methyl 6(S)-E-[2-[(4'-fluoro-3,3',5-trimethyl)[1,1'-biphenyl]-2-yl]ethenyl]-2,2-dimethyl-1,3-dioxane-4(R)acetate; or (4) 2-(β-D-galactosidyl)ethyl 6(S)-E-[2-[(4'-fluoro-3,3',5-trimethyl)[1,1'-biphenyl]-2-yl]ethenyl]-2,2-dimethyl-1,3-dioxane-4(R)acetate.
Claim 9
Dependent Claim
11 words
A compound of Claim 1 wherein R is the group (a).
Claim 10
Dependent Claim
22 words
A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of Claim 1 and a pharmaceutically acceptable carrier.
Claim 11
Dependent Claim
26 words
A composition of Claim 9 wherein the active ingredient is selected from: (1) ethyl 6(S)-E-[2-[(4'-fluoro-3,3',5-trimethyl)-[1,1'-biphenyl]-2-yl]ethenyl]-2,2-dimethyl-1,3-dioxane-4-(R)-acetate; (2) (2,2-dimethyl-1-oxopropoxy)methyl 6-(S)-E-[2-[(4'-fluoro-3,3',5-trimethyl)[1,1'-biphenyl]-2-yl]-ethenyl]-2,2-dimethyl-1,3-dioxane-4(R)-acetate; (3) [5-(1,1-dimethylethyl)-2-oxo-1,3-dioxol-4-yl]-methyl 6(S)-E-[2-[(4'-fluoro-3,3',5-trimethyl)[1,1'-biphenyl]-2-yl]ethenyl]-2,2-dimethyl-1,3-dioxane-4(R)acetate; or (4) 2-(β-D-galactosidyl)ethyl 6(S)-E-[2-[(4'-fluoro-3,3 ,5-trimethyl)[1,1'-biphenyl]-2-yl]ethenyl]-2,2-dimethyl-1,3-dioxane-4(R)acetate.
References Cited (Backward Citations)
No citation records indexed.
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