Computer??Aided Design, Synthesis and Validation of 2??Phenylquinazolinone Fragments as CDK9 Inhibitors with Anti??HIV??1 Tat??Mediated Transcription Activity

…, V Cecchetti, C Pannecouque, A Marcello…

Index: Sancineto, Luca; Iraci, Nunzio; Massari, Serena; Attanasio, Vanessa; Corazza, Gianmarco; Barreca, Maria Letizia; Sabatini, Stefano; Manfroni, Giuseppe; Avanzi, Nilla Roberta; Cecchetti, Violetta; Pannecouque, Christophe; Marcello, Alessandro; Tabarrini, Oriana ChemMedChem, 2013 , vol. 8, # 12 p. 1941 - 1953

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Citation Number: 9

Abstract

Abstract The activity of the cyclin-dependent kinase 9 (CDK9) is critical for HIV-1 Tat- mediated transcription and represents a promising target for antiviral therapy. Here we present computational studies that, along with preliminary synthetic efforts, allowed us to identify and characterize a new class of nontoxic anti-CDK9 chemotypes based on the 2- phenylquinazolinone scaffold. Inhibition of CDK9 translated into the ability to interfere ...