356041-30-0

Upstream product

• 96-72-0 2-chloro-5-nitrobenzenesulfonamide 
• 108-44-1 1-amino-3-methylbenzene 
• 6283-25-6 H₂NC₆H₃(Cl)NO₂ 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of a sulfonylcyanoguanidine as thromboxane A2 receptor antagonist and thromboxane synthase inhibitor

The synthesis and the structure of N-isopropyl-N′-[2-(3′-methylphenylamino)-5-nitrobenzenesulfonyl] urea (14) was drawn from two thromboxane A2 receptor antagonists structurally related to torasemide. Compound 14 showed an IC50 value of 22 nM for the thromboxane A2 (TXA2) receptor of human washed platelets. Compound 14 prevented platelet aggregation induced by arachidonic acid (0.6 mM) and U-46619 (1 μM) with an IC50 value of 0.45 and 0.15 μM, respectively. Moreover, 14 relaxed the rat isolated aorta and guinea-pig trachea precontracted by U-46619, a TXA2 agonist. Its efficacy (IC50) was 20.4 and 5.47 nM, respectively. Finally, 14 (1 μM) completely inhibited TXA2 synthase of human platelets. The pKa value and the crystallographic data of 14 were determined and used to propose an interaction model between the TXA2 antagonists related to torasemide and their receptor.

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

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.