Inhibitor of atherosclerotic intimal thickening

Details Inhibitor of atherosclerotic intimal thickening Inhibitor of atherosclerotic intimal thickening

A - Human Necessities

61

K

A61K 31/44 (2006.01) A61K 31/47 (2006.01)

Patent

CA 2079706

An inhibitor of atherosclerotic intimal thickening, which contains an effective amount of a compound of the formula (I): (see formula I) 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, C1-8 alkyl, C3-7 cycloalkyl, C1-3 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 C1-3 alkyl), trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-tert-butylsilyloxy, hydroxymethyl or -O(CH2)~OR22 (wherein R22 is hydrogen or C1-3 alkyl, and ~ 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, C1-8 alkyl; C2-6 alkenyl, C3-7 cycloalkyl, C5-7 cycloalkenyl or (see formula II) (wherein R7 is hydrogen, C1-8 alkyl, C1-8 alkoxy, C1-3 alkylthio, chloro, bromo, fluoro, chloromethyl, trichloromethyl, trifluoromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-tert-butylsilyloxy or hydroxymethyl); or C1-3 alkyl substituted by one (see formula III) (wherein R7 is as defined above) and zero, one or two C1-3 alkyl; Y is -CH2-, -CH2CH2-, -CH=CH-, -CH2-CH=CH-, -CH=CH-CH2-, -C(CH3)=CH- or -CH=C(CH3)-; Z is -Q-CH2-W-CH2-CO2R12, (see formula IV), (see formula V) or (see formula VI) (wherein Q is -C(O)-, -C(OR13)2- or -CH(OH)-, W is -C(O), -C(OR13)2- or -C(R11)(OH)-, R11 is hydrogen or C1-3 alkyl, R12 is hydrogen, R4 (wherein R14 is alkyl of a chemically or physiologically hydrolyzable alkyl ester moiety, NHR23R24R25 (wherein each Of R23, R24 and R25 is hydrogen or C1-4 alkyl), sodium, potassium or 1/2 calcium), each R13 is independently primary or secondary C1-6 alkyl, or two R13 together form -(CH2)2- or -(CH2)3-, and each of R15 and R16 which are independent of each other, is hydrogen atom or C1-3 alkyl, or R15 and R16 together form -(CH2)2- or -(CH2)3-.

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