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• 106-44-5 p-cresol 
• 96-72-0 2-chloro-5-nitrobenzenesulfonamide 
• 6283-25-6 H₂NC₆H₃(Cl)NO₂ 
• 4533-95-3 5-nitro-2-chlorobenzenesulfonyl chloride 

Relevant academic research and scientific papers

Design, synthesis, and SAR study of a series of N-alkyl-N′-[2- (aryloxy)-5-nitrobenzenesulfonyl]ureas and -cyanoguanidine as selective antagonists of the TPα and TPβ isoforms of the human thromboxane A2 receptor

The prostanoid thromboxane (TX)A2 exerts its proaggregant and constrictive actions upon binding to the specific TXA2 receptor (TP), a member of the G-protein coupled receptor superfamily. In humans, TXA 2 signals through two distinct TP isoforms, TPα and TPβ. Herein, we describe the design, synthesis, and SAR study of a series of original N-alkyl-N′-[2-(aryloxy)-5-nitrobenzenesulfonyl]ureas and -cyanoguanidine. The SAR study was based on the results of a functional assay, TP-mediated intracellular calcium ([Ca2+]i) mobilization performed on the two separate isoforms. Optimal nature and position of several structural moieties was defined for both activity and selectivity toward TPα and TPβ isoforms. Three compounds (9h, 9af, and 9ag), showing increased selectivity for TPβ relative to TPα (23.2:1, 18.1:1, 19.9:1, respectively), were selected for further experiments, and their activity was confirmed in a platelet aggregation assay. This study represents the first extended SAR study dealing with the identification of isoform selective antagonists for the human TXA2 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.