New anti-HIV derivatives: Synthesis and antiviral evaluation

Article abstract of DOI:10.1016/S0968-0896(00)00055-9

A small focused library of 18 compounds incorporating the motif 1,3-(N,N'-dibenzyl)diamino-2-propanol has been synthesized, using adapted synthetic methodologies. These series of compounds were evaluated for their in vitro anti-HIV activity on infected MT₄ cells (syncytium formation observation). Some of the new synthesized compounds show potent anti-HIV activities. EC₅₀ values for compounds (31, 40, 34, 37 and 46Scheme 3(i) Na₂SO₄, CH₂Cl₂, rt; (ii) NaBH₄, EtOH, 0°C; (iii) Boc₂O, CH₂Cl₂, 0°C; (iv) DMSO, TFAA, Et₃N, CH₂Cl₂, -60°C; (v) TFA, CH₂Cl₂, rt; (vi) BOP, RCOOH, Et₃N, CH₂Cl₂, rt.) range from 0.1 to 1μM. In order to determine at which level these new derivatives interfere with the HIV replicative cycle, inhibition assays on recombinant HIV protease and HIV integrase have been performed. None of the compounds were found active on these two enzymatic targets. Experiments are in progress in order to identify their biological target within the HIV replicative cycle. Copyright (C) 2000 Elsevier Science Ltd.