Synthesis and biological evaluation of CHX-DAPYs as HIV-1 non-nucleoside reverse transcriptase inhibitors.

Authors :: Yan ZH
Wu HQ
Chen WX
Wu Y
Piao HR
He QQ
Chen FE
De Clercq E
Pannecouque C
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Jun 15; Vol. 22 (12), pp. 3220-6. Date of Electronic Publication: 2014 Mar 27.
Publication Year :: 2014
Abstract: A series of new diarylpyrimidines (DAPYs) characterized by a halogen atom on the methylene linker between wing I and the central pyrimidine ring was synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. The two most promising compounds 7f and 7g showed excellent activity against wild-type HIV-1 with low nanomolar EC50 values of 0.005 and 0.009 μM, respectively, which were comparable to or more potent than all the reference drugs zidovudine (AZT), lamivudine (3TC), nevirapine (NEV), efavirenz (EFV), delaviridine (DLV) and etravirine (ETV). In particular, 7g also displayed strong activity against the double mutant strain 103N + 181C with an EC50 value of 8.2 μM. The preliminary structure-activity relationship (SAR) and molecular docking analysis of this new series of CHX-DAPYs were also investigated.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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