In our continuing search for novel antiplatelet agents, 4-alkoxy derivative
s of 2-phenylquinoline as well as related compounds were prepared. Through
biological screening, a preliminary structure-antiplatelet activity relatio
nship was established. Compounds 5-ethyl-4-methoxy-2-phenylquinoline (8), 4
-ethoxy-5-ethvl-2-phenylquinoline (9), 4-ethoxycarbonylmethoxy-5-ethyl-2phe
nylquinoline (10), 4-ethoxycarbonylbutoxy-5-ethyl-2-phenylquinoline (12) an
d 5-ethyl-4-(N-ethylcarboxido)methoxy-2-phenyl-quinoline (17) all demonstra
ted potent antiplatelet activity. Among them, compound 8 was the most poten
t with an IC50 value of 0.08 muM and was about 3-fold more active than indo
methacin. The mechanism of antiplatelet action of 8 is possibly through its
inhibition on cyclooxygenase or thromboxane synthetase. (C) 2001 Published
by Elsevier Science Ltd.