METHOD FOR PRODUCING COMPOSITIONS CONTAINING INHIBITOR OF INTIMA THICKENING BEING CAUSA OF ARTERIOSCLEROSIS

摘要

An inhibitor of atherosclerotic intimal thickening, which contains an effective amount of a compound of the formula (I): CHEM wherein ring X is phenyl, substituted phenyl or 5- or 6-membered heterocyclic aryl; each of R1 and R2 which are independent of each other, is hydrogen, C5 PI 3/4 alkyl, C7 PI 1/2 cycloalkyl, C5 PI 7 alkoxy, n-butoxy, i-butoxy, sec-butoxy, tert-butoxy, R20R21N- (wherein each of R20 and R21 which are independent of each other, is hydrogen or C5 PI 7 alkyl), trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-tert-butylsilyloxy, hydroxymethyl or -O(CH6)POR22 (wherein R22 is hydrogen or C5 PI 7 alkyl, and P is 1, 2, or 3); or R1 and R2 together form -CH=CH-CH=CH- or methylenedioxy, when they are at the o-position to each other; R3 is hydrogen, C5 PI 3/4 alkyl, C6 PI 1/4 alkenyl, C7 PI 1/2 cycloalkyl, C psi PI 1/2 cycloalkenyl or CHEM (wherein R7 is hydrogen, C5 PI 3/4 alkyl, C5 PI 3/4 alkoxy, C5 PI 7 alkylthio, chloro, bromo, fluoro, chloromethyl, trichloromethyl, trifluoromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-tert-butylsilyloxy or hydroxymethyl); or C5 PI 7 alkyl substituted by one CHEM (wherein R7 is as defined above) and zero, one or two C5 PI 7 alkyl; Y is -CH6-, -CH6CH6-, -CH=CH-, -CH6-CH=CH-, -CH=CH-CH6-, -C(CH7)=CH- or -CH=C(CH7)-; Z is -Q-CH6-W-CH6-CO6R12, CHEM (wherein Q is -C(O)-, -C(OR13)6- or -CH(OH)-, W is -C(O), -C(OR13)6- or -C(R11)(OH)-, R11 is hydrogen or C5 PI 7 alkyl, R12 is hydrogen, R14 (wherein R14 is alkyl of a chemically or physiologically hydrolyzable alkyl ester moiety, NHR23R24R25 (wherein each of R23, R24 and R25 is hydrogen or C5 PI 8 alkyl), sodium, potassium or 1/2 calcium), each R13 is independently primary or secondary C5 PI 1/4 alkyl, or two R13 together form -(CH6)6- or -(CH6)7-, and each of R15 and R16 which are independent of each other, is hydrogen atom or C5 PI 7 alkyl, or R15 and R16 together form -(CH6)6- or -(CH6)7-.