Discovery of N-aryl-naphthylamines as in vitro inhibitors of the interaction between HIV integrase and the cofactor LEDGF/p75

作者：Crucitti Giuliana Cuzzucoli; Pescatori Luca; Messore Antonella; Madia Valentina Noemi; Pupo Giovanni; Saccoliti Francesco; Scipione Luigi; Tortorella Silvano; Di Leva Francesco Saverio; Cosconati Sandro; Novellino Ettore; Debyser Zeger; Christ Frauke; Costi Roberta^*; Di Santo Roberto

来源：European Journal of Medicinal Chemistry, 2015, 101: 288-294.

DOI：10.1016/j.ejmech.2015.06.036

• Integrase
• LEDGF/p75
• LEDGINs
• N-aryl-naphthylamine

A series of N-aryl-naphthylamines, exemplified by the structures 11-16, were chosen for an in-house library screening to assay their ability to disrupt the interaction between the LEDGF cofactor and the HIV integrase. Structure modification led also to design and synthesize new compounds 17a-f. Compounds 11e,h,k,n, 13b, and 14 showed good activity in AlphaScreen assay. The most active compound lie (IC50 = 2.5 mu M) was selected for molecular modeling studies and showed a binding mode similar to the one of the known LEDGIN 8.

• 出版日期2015-8-28