Benzophenone derivatives of pyrimidines as effective non-nucleoside inhibitors of wild-type and drug-resistant HIV-1 reverse transcriptase

280 Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), one of the most lifeethreatening human diseases [1]. Curr rently, 26 antiretroviral drugs of different nature are used in AIDS therapy. However, due to the high varii ability of the virus genome and the necessity of lifelong treatment, there appear new HIV strains that are resiss tant to existing drugs. For this reason, the developp ment of new effective blockers of virus reproduction, both the wilddtype and the druggresistant forms, is a relevant problem. The majority of existing drugs—synthetic nucleoo side analogues and nonnnucleoside compounds—are reverse transcriptase (RT) inhibitors [2]. The most widely used nonnnucleoside compounds are Viramun® (nevirapine) and Sustiva® (efavirenz), which are ineff fective against a number of druggresistant HIV strains. Among the potential antiiHIV agents, benzophenone derivatives can be distinguished [3, 4]. Recently, we described a series of benzophenone derivatives of pyrii midines that block wilddtype HIVV1 reproduction at nanomolar concentrations. The goal of this work was to study the efficacy of this type of compounds with respect to the druggresistant HIV forms. As a model of viral infection, we used the system based on lentiviral vectors [5]. PseudooHIVV1 viral particles (PVPs) are recombinant lentiviruses carrying a HIVV1 genome fragment devoid of all viral genes but containing the molecules of all its enzymes including RT. PseudooHIVV1 particles also carry the marker gene of the green fluorescent protein, which enables the detection of transduced cells. noxy)ethyl]]5,66dimethyluracyl was synthesized with a 43% yield by the treatment of a fivefold molar excess of 5,66dimethyluracyl with 11bromoo22[22(3,55dimee thylbenzoyl))44chlorophenoxy]ethane in DMFA solution in the presence of К 2 СО 3 .