N-tert-butyl-N'-[5-cyano-2-(4-methylphenoxy)phenylsulfonyl]urea, a new TXA₂ receptor antagonist.

The title compound, C₁₉H₂₁N₃O₄S, crystallizes in the space group P2/c with two molecules in the asymmetric unit. The conformation of both molecules is very similar and is mainly determined by an intramolecular N-H∙∙∙O hydrogen bond between a urea N atom and a sulfonyl O atom. The O and second N atom of the urea groups are involved in dimer formation via N-H∙∙∙O hydrogen bonds.

Synthesis and pharmacological evaluation of 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as novel thromboxane A₂ receptor antagonists.

New series of original 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas were synthesized and evaluated as thromboxane A2 receptor (TP receptor) antagonists. A functional pharmacological test was used, which consisted of measuring the inhibition of intracellular calcium mobilization in a model of mammalian cell line that specifically over-expressed the individual TPα or TPβ isoforms. 2-Arylamino-5-cyanobenzenesulfonylureas exhibited virtually identical affinity and/or functional activity than 2-aryloxy-5-cyanobenzenesulfonylureas for both TPα and TPβ, but some 2-aryloxy-substituted compounds showed increased selectivity for TPβ relative to TPα.