Antiplatelet actions of 2-(4-[1-(2-chlorophenyl) piperazinyl]) methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one compound.
The new quinazolinone derivative, 2-(4-[1-(2-chlorophenyl)piperazinyl]) methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(CK53 ), inhibited platelet aggregation and ATP release induced by arachidonic acid, collagen, PAF and U46619 in washed rabbit platelets. In human platelet-rich plasma CK53 also significantly suppressed the platelet aggregation and ATP release challenged by epinephrine and ADP. The thromboxane B2 formation of rabbit washed platelets caused by collagen and thrombin was reduced by CK53 but that induced by arachidonic acid. CK53 inhibited the intracellular calcium increase stimulated by collagen and thrombin in quin-2/AM-loaded rabbit platelets. Phosphoinositides breakdown caused by collagen, U46619, PAF and thrombin was inhibited by CK53. CK53 also suppressed the aggregation of elastase-treated human platelets induced by fibrinogen but no alteration in platelet cyclic-AMP level. In conclusion, these data indicate that antiplatelet effect of CK53 may be mainly due to the direct inhibition of phosphoinositides breakdown.
Ding
Y A
YA
Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Chou
T C
TC
Chern
J W
JW
Yen
M H
MH
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000097:blood; D003094:Collagen / Q000037:antagonists & inhibitors; D000242:Cyclic AMP / Q000097:blood; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005340:Fibrinogen / Q000037:antagonists & inhibitors; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010196:Pancreatic Elastase / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000097:blood; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D013929:Thromboxane B2 / Q000096:biosynthesis
C093393:CK 53; D007093:Imidazoles; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; D011799:Quinazolines; D011956:Receptors, Cell Surface; D016718:Arachidonic Acid; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D005340:Fibrinogen; D003094:Collagen; D000242:Cyclic AMP; D010196:Pancreatic Elastase; D002118:Calcium; D004837:Epinephrine