N,N-Dialkyl-2-phenylindol-3-ylglyoxylamides. A New Class of Potent and Selective Ligands at the Peripheral Benzodiazepine Receptor

摘要

We report the synthesis and the affinity data at both the peripheral (PBR) and the central benzodiazepine receptors of a series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamide derivatives III, designed as conformationally constrained analogues of 2-phenylindole-3-acetamides II such as FGIN-1-27. Most of the new compounds showed a high specificity and affinity for PBR, with K_i in the nanomolar to subnanomolar range. The most potent ligands (4-7, 9, 13-27) stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to or higher than that of classical ligands. The SARs of this new class of compounds are discussed.