Discovery of Thiophene[3,2-d]pyrimidine Derivatives as Potent HIV-1 NNRTIs Targeting the Tolerant Region I of NNIBP.

ABSTRACT: Our previous studies led us to conclude that thiophene[3,2-d]pyrimidine is a promising scaffold for diarylpyrimidine (DAPY)-type anti-HIV agents with potent activity against resistance-associated human immunodeficiency virus (HIV) variants (J. Med. Chem. 2016, 59, 7991-8007; J. Med. Chem. 2017, 60, 4424-4443). In the present study, we designed and synthesized a series of thiophenepyrimidine derivatives with various substituents in the right wing region of the structure with the aim of developing new interactions with the tolerant region I of the binding pocket of the HIV-1 non-nucleoside reverse transcriptase (NNRTI), and we evaluated their activity against a panel of mutant HIV-1 strains. All the derivatives exhibited moderate to excellent

SUBMITTER: Kang D 

PROVIDER: S-EPMC5683699 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature