EP0283217A1
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Novel antihypercholesterolemic compounds
Assignee: Merck and Co Inc
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Filing: 1988-03-11
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Granted: —
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Expires: 2008-03-11
Abstract
Abstract Novel antihypercholesterolemic compounds of structure (I) or (II), pharmaceutically acceptable salts thereof, and a novel process for preparing compounds of structure I, are disclosed.
Inventors
- 👤 Gerald E. Stokker
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 01:50
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/16; C07D309/28; C07D309/30; A; A61; A61P; A61P3/00; A61P3/06
Claims Analysis
Total Claims: 10
Claim 1
Independent Claim
153 words
A compound of structural formula (I) or (II): wherein Z is phenyl, naphthyl, thiophenyl, thiazyl, pyrryl; or phenyl, naphthyl, thiophenyl, thiazyl, pyrryl substituted with a group A; A is selected from a group consisting of: Cl, F, OH, C₁₋₅alkyl, C₁₋₅alkyloxy, C₂₋₈alkanoyloxy, C₂₋₆alkanoylamino, C₁₋₅alkyloxycarbonyl, phenyl, hydroxy-C₁₋₅alkyl, trifluromethyl-C₂₋₈alkanoylamino; E is a direct bond, -CH₂-, -CH₂CH₂- R₁, R₂ and R₃ are each selected from: H, Cl, or F, C₁₋₄alkyl, C₁₋₄chloroalkyl or C₁₋₄fluroalkyl, phenyl, phenyl substituted by Cl or F, C₁₋₄alkyloxy, C₂₋₈alkanoyloxy, C₂₋₈alkanoyloxy-C₁₋₅ alkyl, and OR₄ in which R₄ is H, C₂₋₈alkanoyl, benzoyl phenyl, chlorophenyl or flurophenyl, phenyl-C₁₋₃alkyl, C₁₋₈alkyl, C₁₋₄chloroalkyl or C₁₋₄fluroalkyl, cycloalkyl-C₁₋₃alkyl, adamantyl-C₁₋₃alkyl, or substituted phenyl-C₁₋₃alkyl in which the substituents are selected from: chlorine or fluorine, C₁₋₄alkyloxy, C₁₋₄alkyl, C₁₋₄chloroalkyl or C₁₋₄fluroalkyl; R₅ is hydrogen, C₁₋₅ alkyl or C₁₋₅ alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino; and a pharmaceutically acceptable salt of the compound (II) in which R₅ is hydrogen.
Claim 2
Dependent Claim
153 words
A compound of structural formula (I) or (II): wherein Z is phenyl, naphthyl, thiophenyl, thiazyl, pyrryl; or phenyl, naphthyl, thiophenyl, thiazyl, pyrryl substituted with a group A; A is selected from a group consisting of: Cl, F, OH, C₁₋₅alkyl, C₁₋₅alkyloxy, C₂₋₈alkanoyloxy, C₂₋₆alkanoylamino, C₁₋₅alkyloxycarbonyl, phenyl, hydroxy-C₁₋₅alkyl, trifluromethyl-C₂₋₈alkanoylamino; E is a direct bond, -CH₂-, -CH₂CH₂- R₁, R₂ and R₃ are each selected from: H, Cl, or F, C₁₋₄alkyl, C₁₋₄chloroalkyl or C₁₋₄fluroalkyl, phenyl, phenyl substituted by Cl or F, C₁₋₄alkyloxy, C₂₋₈alkanoyloxy, C₂₋₈alkanoyloxy-C₁₋₅ alkyl, and OR₄ in which R₄ is H, C₂₋₈alkanoyl, benzoyl phenyl, chlorophenyl or flurophenyl, phenyl-C₁₋₃alkyl, C₁₋₈alkyl, C₁₋₄chloroalkyl or C₁₋₄fluroalkyl, cycloalkyl-C₁₋₃alkyl, adamantyl-C₁₋₃alkyl, or substituted phenyl-C₁₋₃alkyl in which the substituents are selected from: chlorine or fluorine, C₁₋₄alkyloxy, C₁₋₄alkyl, C₁₋₄chloroalkyl or C₁₋₄fluroalkyl; R₅ is hydrogen, C₁₋₅ alkyl or C₁₋₅ alkyl substituted with a member of the group consisting of phenyl, dimethylamino, or acetylamino; and a pharmaceutically acceptable salt of the compound (II) in which R₅ is hydrogen.
Claim 3
Dependent Claim
53 words
A compound of Claim 1 wherein: Z is phenyl or thiophenyl; or phenyl substituted with a group A; E is -CH₂CH₂- ; and A is selected from a group consisting of: OH, C₁₋₅alkyloxy C₁₋₅alkyloxycarbonyl, C₂₋₈ alkanoyloxy, phenyl, trifluromethyl-C₂₋₈alkanoylamino, hydroxy C₁₋₅alkyl; and R₁, R₂ and R₃ are each selected from: H, Cl or F.
Claim 4
Dependent Claim
65 words
A compound of Claim 2, selected from the group wherein: R₁ is hydrogen, R₂ and R₃ are each chloro in the 2 and 4 positions; R₅ is H and a. Z is phenyl, b. Z is 4-C₆H₅-C₆H₄-, c. Z is 4-CH₃O-C₆H₄-, d. Z is 4-HO-C₆H₄-, e. Z is 2-HO-CH₂C₆H₄-, f. Z is 4-CH₃O₂C-C₆H₄-, g. Z is 4-F₃CCO₂NH-C₆H₄-, h. Z is 3-CH₃O-C₆H₄-, i. Z is 3-thiophenyl.
Claim 5
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 6
Dependent Claim
44 words
A hypocholesterolemic, hypolipidemic pharmaceutical composition comprising a nontoxic therapeutically effective amount of a compound of Claim 1 in combination with a pharmaceutically acceptable nontoxic cationic polymer capable of binding bile acids in a non-reabsorbable form in the gastrointestinal tract and a pharmaceutically acceptable carrier.
Claim 7
Dependent Claim
21 words
The use of a compound as claimed in Claim 1 in the manufacture of a medicament useful for inhibiting cholesterol biosynthesis.
Claim 8
Dependent Claim
73 words
A process for the preparation of a compound as claimed in Claim 1 which comprises contacting a compound of formula Z - I (wherein Z is as defined in Claim 1) with a compound of structure IV (wherein R₁, R₂, R₃ and E are as defined in Claim 1) in the presence of a Pd[0] catalyst and a trialkylamine wherein the trialkylamine has at least one hydrogen on the alpha or beta position.
Claim 9
Dependent Claim
13 words
A process as claimed in Claim 7 in which the trialkylamine is triethylamine.
Claim 10
Dependent Claim
17 words
A process as claimed in Claim 7 or Claim 8 in which the palladium catalyst is tetrakis(triphenylphosphine)palladium.
References Cited (Backward Citations)
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