184576-52-1Relevant academic research and scientific papers
Potent dibasic GPIIb/IIIa antagonists with reduced prolongation of bleeding time: Synthesis and pharmacological evaluation of 2-oxopiperazine derivatives
Kitamura,Fukushi,Miyawaki,Kawamura,Konishi,Terashita,Naka
, p. 2438 - 2450 (2007/10/03)
A series of 2-oxopiperazine derivatives, possessing basic moieties at the 3- and the 4-positions, were synthesized and evaluated for their abilities to inhibit platelet aggregation and for their effects on bleeding time. Among the compounds, 2-[(3S)-4-[2-[(4-guanidinobenzoyl)amino] acetyl]3-[3-[(4-guanidinobenzoyl)amino]propyl]-2-oxopiperazinyl]acetic acid (12c) showed a potent inhibitory effect on platelet aggregation and good dissociation between the efficacy and the bleeding side effect. Intravenous infusion of compound 12c at 1.6 μg/mL/min. completely prevented arterial thrombus formation induced by endothelial injury in guinea pigs. The dose of 12c that prolonged the bleeding time to three times the control value was 5.8/μg/mL/min. These results suggest that compound 12c might be useful in the clinical treatment of thrombotic diseases, and we selected 12c (TAK-024) as a candidate for the clinical trials.
