899790-32-0Relevant academic research and scientific papers
Synthesis and pharmacological evaluation of novel nitrobenzenic thromboxane modulators as antiplatelet agents acting on both the alpha and beta isoforms of the human thromboxane receptor
Hanson, Julien,Reynaud, Denis,Qiao, Na,Devel, Philippe,Moray, Anne-Lise,Renard, Jean-Fran?ois,Kelley, Leanne P.,Winum, Jean-Yves,Montero, Jean-Louis,Kinsella, B. Therese,Pirotte, Bernard,Pace-Asciak, Cecil R.,Dogné, Jean-Michel
, p. 3701 - 3709 (2007/10/03)
Thromboxane A2 (TXA2) is an arachidonic acid metabolite involved in pathologies such as stroke, myocardial infarction, and atherosclerosis. Consequently, the design of TXA2 receptor (TP) antagonists remains of great interest in cardiovascular medicine. The actions of TXA2 are mediated by its specific G-protein coupled receptor of which two alternative spliced isoforms, TPα and TPβ, have been described in humans. In this study, we report the synthesis of a series of original N-alkyl-N′-[2-(cycloalkyl, alkylaryl)-5-nitrobenzenesulfonyl]urea and N-alkyl-N′-[2-(alkylaryl)-5-nitrobenzenesulfonyl]-N″- cyanoguanidines and outline their pharmacological evaluation using the individual TPα and TPβ isoforms. Among compounds analyzed, several of them exhibited greater affinity and/or functional activity for either TPα or TPβ. The most promising molecules were also found to be antiplatelet agents. From the present results, structural features involved in isoform selectivity can be proposed, and thereby several lead compounds have been identified for the further development of selective TP isoform antagonists.
