Substituted azetidinone compounds useful as hypocholesterolemic agents (hypocholesterolemic agents useful as hypocholesterolemic agents)

摘要

The present invention relates to a substituted azetidinone hypocholesterolemid of the formula (1) or a pharmaceutically acceptable salt thereof:;Wherein Ar^OneR³-substituted aryl; Ar²R⁴-substituted aryl; Ar³R⁵-substituted aryl; Y and Z are independently-CH₂-,-CH (lower alkyl)-, and-C (lower alkyl)-; A is-O-,-S-,-S (O)-or-S (O)₂-ego; R^One-OR⁶,-O (CO) R⁶-,-O (CO) OR⁹And-O (CO) NR⁶R⁷And R is selected from the group consisting of R²Is selected from the group consisting of hydrogen, lower alkyl and aryl, or R^OneAnd R²= O together; q is 1, 2 or 3; p is 0, 1, 2, 3 or 4; R⁵Is independently-OR⁶,-O (CO) R⁶,-O (CO) OR⁹,-O (CH₂)_1-5OR⁹,-O (CO) NR⁶R⁷,-NR⁶R⁷,-NR⁸(CO) R⁷,-NR⁶(CO) OR⁹,-NR⁶(CO) NR⁷R⁸,-NR⁶SO²-lower alkyl,-NR ⁸SO₂-aryl,-CONR⁶R⁷,-COR⁶,-SO₂NR⁶R⁷, S (O)_0-2-alkyl, S (O)_0-2Aryl,-O (CH₂)_1-10-COOR⁶,-O (CH₂)_0-10-CONR⁶R⁷, o-halogeno, m-halogeno, o-lower alkyl, m-lower alkyl,-(lower alkylene)-COOR⁸And-CH = CH-COOR⁸ RTI ID = 0.0 1 /RTI to 3 substituents selected from the group consisting of R³And R⁴Are independently R⁵, Hydrogen, p-lower alkyl, aryl,-NO₂,-CF₃And p-halogeno; and R 3 R⁶, R⁷And R⁸Are independently selected from the group consisting of hydrogen, lower alkyl, aryl and aryl-substituted lower alkyl; R⁹Is lower alkyl, aryl or aryl-substituted lower alkyl.;The present invention also relates to a method for reducing cholesterol in serum by administering the above compound, a pharmaceutical composition containing the same, a combination of a substituted azetidinone and a cholesterol biosynthesis inhibitor for the prevention and treatment of atherogenesis, Intermediates, and methods of making such intermediates.