A series of AT₂R ligands have been synthesized applying a quick, simple, and safe transesterification-type reaction whereby the sulfonyl carbamate alkyl tail of the selective AT₂R antagonist C38 was varied. Furthermore, a limited number of compounds where acyl sulfonamides and sulfonyl ureas served as carboxylic acid bioisosteres were synthesized and evaluated. By reducing the size of the alkyl chain of the sulfonyl carbamates, ligands 7a and 7b were identified with significantly improved in vitro metabolic stability in both human and mouse liver microsomes as compared to C38 while retaining the AT₂R binding affinity and AT₂R/AT₁R selectivity. Eight of the compounds synthesized exhibit an improved stability in human microsomes as compared to C38.

已经应用快速，简单和安全的酯交换型反应合成了一系列AT ₂ R配体，从而改变了选择性AT ₂ R拮抗剂C38的磺酰氨基甲酸酯烷基尾。此外，合成并评估了其中酰基磺酰胺和磺酰脲用作羧酸生物等排体的有限数量的化合物。通过减少磺酰氨基甲酸酯烷基链的大小，鉴定出配体7a和7b与C38相比在人和小鼠肝微粒体中具有明显改善的体外代谢稳定性，同时保留了AT ₂ R结合亲和力和AT ₂ R /在₁R选择性。与C38相比，合成的八种化合物在人微粒体中显示出更高的稳定性。