The effect of carbamoylpiperidine and nipecotoylpiperazine analogs on ADP-stimulated human thrombocyte aggregation and platelet factor 3 availability.
There is a striking congruence between the inhibitory effects of three synthetic entities on ADP-induced (i) human blood platelet aggregation and (ii) platelet factor 3 availability as evidenced by prolonged 'Stypven time'. The pronounced parallel between each compound's potency in inhibiting aggregation (e.g. IA 48.9 +/- 1.3, S.E., %; n = 16) and in impeding platelet factor 3 availability (e.g. IPF-3av 42.3 +/- 2.5, S.E., %; n = 12), determined concurrently in platelet-rich plasma of four different donors, further substantiates that the antiplatelet activity of our carbamoylpiperidine and nipecotoylpiperazine congeners is exerted through their interaction with anionic phospholipids.
Dillingham
E O
EO
Department of Medicinal Chemistry, University of Tennessee, Memphis 38163.
Lasslo
A
A
Gollamudi
R
R
Bond
S E
SE
Carter-Burks
G
G
D000244:Adenosine Diphosphate / Q000502:physiology*; D000328:Adult; D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism*; D006801:Humans; D008297:Male; D009557:Nipecotic Acids / Q000378:metabolism / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D010879:Piperazines; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010977:Platelet Factor 3 / Q000378:metabolism*
D001779:Blood Coagulation Factors; D009557:Nipecotic Acids; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; C043099:alpha, alpha'-bis(3-(N,N-diethylcarbamoyl)piperidino)-4-xylene; D010977:Platelet Factor 3; D000244:Adenosine Diphosphate; C063977:1,10-bis(3-(N,N-diethylcarbamoyl)piperidino)decane; C063976:N,N'-bis(1-decylnipecotoyl)piperazine