4-aryl-3-(heteroarylureido)-1,2-dihydro-2-oxo-quinoline derivative as a therapeutic agent for hypercholesterolemia and atherosclerosis (4-ARYL-3-(HETEROARYLUREIDO) DIHYDRO-2-OXO-QUINOLINE DERIVATIVES AS ANTIHYPERCHOLESTEROLEMIC AND ANTIATHEROSCLEROTIC AGENTS)

摘要

The present invention relates to compounds of the general formula (I), or a pharmaceutically acceptable salt thereof, and the following general formula (IV) intermediates used in the synthesis of said compounds.;Wherein each m is independently 0 to 4; R²Is hydrogen and (C_One-C₆) Alkyl, and R³And R⁴Each independently selected from the group consisting of halogen, RTI ID = 0.0 (C_One-C₆) Alkyl, optionally substituted with one or more halogen atoms (C_One-C₆) Alkoxy, optionally substituted with one or more halogen atoms (C_One-C₆) Alkylthio, nitro, (C_One-C₆) Carboxyl optionally hydroxylated with an alkyl group, hydroxyl, (C_One-C₄) Acyloxy and (C_One-C₃) /RTI acyl; X is sulfur or oxygen; Q represents a general formula;Wherein m is as defined above, n is 0 or 1, 1 is each independently 0 to 3, R⁶And R⁷Are each halogen, (C_One-C₆) Alkyl, (C_One-C₆) Haloalkyl, optionally halogenated (C_One-C₆) Alkoxy, (C_One-C₆) Alkylthio, (C₅-C₇) Cycloalkylthio, optionally substituted phenyl (C_One-C₆) Alkylthio, substituted phenylthio, heteroarylthio, heteroaryloxy, (C_One-C₆) Alkylsulfonyl, (C_One-C₆) Alkylsulfonyl, (C₅-C₇) Cycloalkylsulfinyl, (C₅-C₇) Cycloalkylsulfonyl, phenyl (C_One-C₆) Alkylsulfinyl, phenyl (C_One-C₆) Alkylsulfonyl, substituted phenylsulfinyl, substituted phenylsulfonyl, heteroarylsulfinyl, heteroarylsulfonyl, and NR¹⁰R¹¹[Wherein R¹⁰And R¹¹Are the same or different and represent hydrogen, (C_One-C₆) Alkyl, optionally substituted phenyl, (C_One-C₆) Acyl and optionally substituted aroyl wherein the substituted phenyl and substituted aroyl groups are (C_One-C₆) Alkyl, (C_One-C₆) Alkoxy, (C_One-C₆) Alkylthio, halogen and trifluoromethyl), or is selected from the group consisting of R RTI ID = 0.0 ¹⁰And R¹¹Together with the nitrogen to which they are attached form a piperidine, pyrrolidine or morpholine ring, and is selected from the group consisting of nitrogen and carbon of B, D, E and G, with the proviso that B , When at least one of D and E is nitrogen and G is nitrogen, the group of the general formula (XVI) is bonded to the nitrogen of the general formula (I) in the 4-position or the 5-position (denoted a and b) of the pyrimidine ring , Wherein the optional nitrogen may be oxidized.;The compound of formula (I) is an inhibitor of acyl-CoA A: cholesterol acyltransferase (ACAT) and is useful as a therapeutic agent for hypolipidemia and atherosclerosis.