TY - JOUR
T1 - 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyluracils as potent anti-HIV-1 agents
AU - Novikov, Mikhail S.
AU - Ivanova, Olga N.
AU - Ivanov, Alexander V.
AU - Ozerov, Alexander A.
AU - Valuev-Elliston, Vladimir T.
AU - Temburnikar, Kartik
AU - Gurskaya, Galina V.
AU - Kochetkov, Sergey N.
AU - Pannecouque, Christophe
AU - Balzarini, Jan
AU - Seley-Radtke, Katherine L.
N1 - Funding Information:
This work was supported by Ministry of Education and Science of Russian Federation (state contract 16.512.11.2192), by the Russian Foundation for Basic Research (grant 10-04-0056), by the Presidium of the Russian Academy of Sciences (Programme ‘Molecular and Cellular Biology’) and by the K. U. Leuven (GOA no. 10/014). A.I. was supported by grant of President of Russian Federation (МК-5035.2011.4). The authors like to thank Inna Karpenko and Natalia Zakirova (EIMB), and Lizette van Berckelaer, Kristien Minner and Kris Uyttersprot (Rega) for their dedicated technical assistance.
PY - 2011/10/1
Y1 - 2011/10/1
N2 - Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus, the candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms.
AB - Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus, the candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms.
KW - Benzophenone
KW - HIV-1
KW - Non-nucleoside reverse transcriptase inhibitors
KW - Reverse transcriptase
KW - Uracil
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U2 - 10.1016/j.bmc.2011.08.025
DO - 10.1016/j.bmc.2011.08.025
M3 - Article
C2 - 21903401
AN - SCOPUS:80052950104
SN - 0968-0896
VL - 19
SP - 5794
EP - 5802
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 19
ER -