1421044-95-2Relevant academic research and scientific papers
Discovery of piperidine-linked pyridine analogues as potent non-nucleoside HIV-1 reverse transcriptase inhibitors
Chen, Xuwang,Li, Yuanyuan,Ding, Shufang,Balzarini, Jan,Pannecouque, Christophe,DeClercq, Erik,Liu, Huiqing,Liu, Xinyong
, p. 1117 - 1126 (2013/07/26)
In our continued efforts to discover more active and less toxic HIV-1 non-nucleoside reverse transcriptase inhibitors, we recently designed a novel series of piperidine-linked pyridine analogues on the basis of diarylpyrimidine derivatives, among which two drugs-etravirine and rilpivirine-are approved for use by the US FDA. The title compounds were evaluated for activity against wild-type and resistant mutant strains of HIV-1 as well as HIV-2 in MT-4 cells. The highly potent compound BD-c1 (EC50=10nM, CC50≥146μM, SI≥14126) displays lower cytotoxicity and higher selectivity than etravirine (EC50=2.2nM, CC50=28μM, SI=12884) against wild-type HIV-1. Compound BD-e2 (EC50=5.1nM) shows greater antiviral efficacy against wild-type HIV-1 than do the four reference drugs nevirapine, delavirdine, efavirenz, and zidovudine. Many compounds were also found to be active against the frequently observed drug-resistant double mutant (K103N+Y181C) HIV-1 strain. Herein we report the design, synthesis, anti-HIV evaluation, preliminary structure-activity relationships, and molecular simulations of novel piperidine-linked pyridine analogues.
