1189790-64-4

Upstream product

• 10570-67-9 4-iodo-2,6-dimethylphenol 
• 1189790-59-7 4-[4-(4-{3-[2-(2-{2-[2-(prop-2-ynyloxy)ethoxy]ethoxy}ethoxy)-ethoxy]prop-1-ynyl}-2,6-dimethylphenoxy)pyrimidin-2-ylamino]benzonitrile 
• 1189790-58-6 4-(4-{4-[3-(2-{2-[2-(2-hydroxyethoxy)ethoxy]ethoxy}ethoxy)prop-1-ynyl]-2,6-dimethylphenoxy}pyrimidin-2-ylamino)benzonitrile 
• 1189790-57-5 4-((4-(4-iodo-2,6-dimethylphenoxy)pyrimidin-2-yl)amino) benzonitrile 
• 244768-32-9 4-[(4-chloro-2-pyrimidinyl)amino]benzonitrile 
• 1189790-62-2 d4T-4PEG-TMC 
• 1189790-60-0 C₃₇H₄₀N₄O₈S 

Relevant academic research and scientific papers

Bifunctional inhibition of human immunodeficiency virus type 1 reverse transcriptase: Mechanism and proof-of-concept as a novel therapeutic design strategy

Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is a major target for currently approved anti-HIV drugs. These drugs are divided into two classes: nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs). This study illustrates the synthesis and biochemical evaluation of a novel bifunctional RT inhibitor utilizing d4T (NRTI) and a TMC-derivative (a diarylpyrimidine NNRTI) linked via a poly(ethylene glycol) (PEG) linker. HIV-1 RT successfully incorporates the triphosphate of d4T-4PEG-TMC bifunctional inhibitor in a base-specific manner. Moreover, this inhibitor demonstrates low nanomolar potency that has 4.3-fold and 4300-fold enhancement of polymerization inhibition in vitro relative to the parent TMC-derivative and d4T, respectively. This study serves as a proof-of-concept for the development and optimization of bifunctional RT inhibitors as potent inhibitors of HIV-1 viral replication.