Synthesis of 2,3-disubstituted 1,4-naphthoquinones as antiplatelet agents.
In continuing search for novel antiplatelet agents, the highly potent agent 2-chloro-3-methoxycarbonylethylcarboxamido-1,4-naphthoquinone 2 was selected as lead compound. Structure-activity relationships in this series were examined. Some of these compounds showed significant antiplatelet activities. Further studies on the action mechanism showed that 2-acetamido-3-chloro-1,4-naphthoquinone 4 has a direct inhibitory action on cytosolic phospholipase A(2) (cPLA(2)) activity in platelets.
Lien
Jin-Cherng
JC
Graduate Institute of Chinese Pharmaceutical Sciences, Taichung, Taiwan, R.O.C. jclien@mail.cmu.edu.tw
Wu
Chi-Rei
CR
Hour
Mann-Jen
MJ
Huang
Li-Jiau
LJ
Huang
Tur-Fu
TF
Kuo
Sheng-Chu
SC
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015195:Drug Design; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009285:Naphthoquinones; D010975:Platelet Aggregation Inhibitors; D054510:Phospholipases A2, Cytosolic