Synthesis of 4-alkoxy-2-phenylquinoline derivatives as potent antiplatelet agents.
In our continuing search for novel antiplatelet agents, 4-alkoxy derivatives of 2-phenylquinoline as well as related compounds were prepared. Through biological screening, a preliminary structure antiplatelet activity relationship was established. Compounds 5-ethyl-4-methoxy-2-phenylquinoline (8), 4-ethoxy-5-ethyl-2-phenylquinoline (9), 4-ethoxycarbonylmethoxy-5-ethyl-2-phenylquinoline (10), 4-ethoxycarbonylbutoxy-5-ethyl-2-phenylquinoline (12) and 5-ethyl-4-(N-ethylcarboxido)methoxy-2-phenylquinoline (17) all demonstrated potent antiplatelet activity. Among them, compound 8 was the most potent with an IC50 value of 0.08 microM and was about 3-fold more active than indomethacin. The mechanism of antiplatelet action of 8 is possibly through its inhibition on cyclooxygenase or thromboxane synthetase.
Ko
T C
TC
Graduate Institute of Pharmaceutical Chemistry, China Medical College, Taichung, Taiwan.
Hour
M J
MJ
Lien
J C
JC
Teng
C M
CM
Lee
K H
KH
Kuo
S C
SC
Huang
L J
LJ
D000473:Alkanes / Q000138:chemical synthesis / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D010972:Platelet Activating Factor / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000494:pharmacology
D000473:Alkanes; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011804:Quinolines; D016718:Arachidonic Acid; D003094:Collagen; D013917:Thrombin