当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis.

Anxiolytic-like effects of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides by modulation of translocator protein promoting neurosteroid biosynthesis.

Abstract：

:Novel N,N-disubstituted indol-3-ylglyoxylamides (1-56), bearing different combinations of substituents R 1-R 5, were synthesized and evaluated as ligands of the translocator protein (TSPO), the 18 kDa protein representing the minimal functional unit of the "peripheral-type benzodiazepine receptor" (PBR). Most of the new compounds showed a nanomolar/subnanomolar affinity for TSPO and stimulated steroid biosynthesis in rat C6 glioma cells with a potency similar to or higher than that of classic TSPO ligands such as PK 11195. Moreover, when evaluated in vivo by means of the elevated-plus-maze (EPM) paradigm in the rat, compound 32, the best-performing derivative in terms of TSPO affinity and pregnenolone production, showed clear anxiolytic effects. The results of this study suggested that the novel N,N-disubstituted indol-3-ylglyoxylamides may represent a promising class of compounds potentially suited for the treatment of anxiety disorders.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Da Settimo F,Simorini F,Taliani S,La Motta C,Marini AM,Salerno S,Bellandi M,Novellino E,Greco G,Cosimelli B,Da Pozzo E,Costa B,Simola N,Morelli M,Martini C

doi

10.1021/jm8003224

subject

Has Abstract

pub_date

2008-09-25 00:00:00

pages

5798-806

issue

18

eissn

0022-2623

issn

1520-4804

journal_volume

51

pub_type

杂志文章

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