| 摘要 |
4-¢(Heterocycloalkyl or heteroaromatic)-substituted phenyl!-2-azetidinone hypocholesterolemic agents of formula (I) or a pharmaceutically acceptable salt thereof, wherein: A is optionally substituted heterocycloalkyl, optionally substituted heteroaryl, optionally substituted benzofused heterocycloalkyl, or optionally substituted benzofused heteroaryl; Ar1 is optionally substituted aryl; Ar2 is optionally substituted aryl; Q is a bond or, with the 3-position ring carbon of the azetidinone, forms the spiro group (a); and R1 is selected from the group consisting of -(CH2)q-, wherein q is 26, provided that when Q is a spiro ring, q can also be 0 or 1; -(CH2)e-G- (CH2)r-, wherein G is -O-, -C(O)-, phenylene, -NR8- or -S(O)0-2-, e is 0-5 and r is 0-5, provided that the sum of e and r is 1-6; alkenylene; and -(CH2)f-V- (CH2)g-, wherein V is cycloalkylene, f is 1-5 and g is 0-5, provided that the sum of f and g is 1-6; R5 is (b), (c), (d), (e), (f), (g) or (h); R6 and R7 are -CH2-, -CH(alkyl)-, -C(dialkyl), -CH=CH- or -C(alkyl)=CH-; or R5 together with an adjacent R6, or R5 together with an adjacent R7, form a -CH=CH- or a CH=C(alkyl)- group; a and b are independently 0-3, provided both are not zero; and when Q is a bond, R1 also can be: (i), (j) or (k); M is -O-, -S-, -S(O)-or -S(O)2-; X, Y and Z are -CH2-, -CH(alkyl)- or -C(dialkyl); R10 and R12 OR14, -O(CO)R14, -O(CO)OR16 or -O(CO)NR14R15; R11 and R13 are H, alkyl or aryl; or R10 and R11 together are =O, or R12 and R13 together are =O; d is 13; h is 0-4; s is 0 or 1; t is 0 or 1; m, n and p are independently 0-4; provided that at least one of s and t is 1, and the sum of m, n, p, s and t is 1-6; provided that when p is 0 and t is 1, the sum of m, s and n is 1-5; and provided that when p is 0 and s is 1, the sum of m, t and n is 1-5; v is 0 or 1; j and k are independently 1-5, provided that the sum of j, k and v is 1-5; R8 is H, alkyl, arylalkyl, -C(O)R14 or -COOR14; R9 is H, alkyl, alkoxy, -COOH, NO2, -NR14R15, OH or halogeno; R14 and R15 are H, alkyl, aryl and arylalkyl; R16 is alkyl or optionally substituted aryl; and R19 is H, OH or alkoxy are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, pharmaceutical compositions containing them, and the combination of a substituted azetidinone and a cholesterol biosynthesis inhibitor for the treatment and prevention of atherosclerosis.
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