Synthesis and anti-HIV activity of some [Nucleoside Reverse Transcriptase Inhibitor]-C5′-linker-[Integrase Inhibitor] heterodimers as inhibitors of HIV replication

Abstract

Selected for their expected ability to inhibit HIV replication, a series of eight heterodimers containing a Nucleoside Reverse Transcriptase Inhibitor (NRTI) and an Integrase Inhibitor (INI), bound by a linker, were designed and synthesized. For the NRTIs, d4U, d2U and d4T were chosen. For the INIs, 4-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]-2,4-dioxobutyric acid (6) and 4-(3,5-dibenzyloxyphenyl)-2,4-dioxobutyric acid (9) (belonging to the β-diketo acids class) were chosen. The conjugation of the two different inhibitors (NRTI and INI) was performed using an amino acid (glycine or β-alanine) as a cleavable linker. © 2004 Taylor & Francis Ltd.