4,4-Disubstituted-3,4-dihydro-2(1H)-quinazolinones as HIV reverse transcriptase inhibitors

Abstract

Human immunodeficiency virus (HIV) infection represents a serious medical problem, successfully approached ultimately by the introduction of highly active antiretroviral therapy (HAART). One of the classes of drugs present in many HAART regimens is constituted by the non-nucleoside reverse transcriptase inhibitors (NNRTIs), with three clinical drugs available at present (nevirapine, delavirdine and efavirenz) and many other derivatives in advanced clinical trials. NNRTIs successfully block HIV-1 infection by binding to the enzyme reverse transcriptase (RT) at an allosterically located, non-substrate binding site. However, mutations of this protein easily lead to drug-resistant viral strains. In this patent, Bristol-Myers Squibb presents a new class of NNRTIs obtained using efavirenz as the lead molecule, which also seem to be effective against HIV isolates resistant to the three clinically used drugs belonging to this class of pharmacological agents. Efavirenz is not only highly effective in various HAART regimens, but it is also the first anti-HIV drug with administration once-a-day. Drugs similar to efavirenz, but also effective against resistant viral strains, will lead to fundamental advances in the treatment and prevention of this disease.

• antiviral agent
• efavirenz
• HIV
• non-nucleoside reverse transcriptase inhibitor (NNRTI)
• quinazolinone
• reverse transcriptase inhibition