Synthesis and anti-HIV Activity of a Series of 2-Indolinones and Related Analogues

A novel series of 2-indolinones with in vitro anti-HIV (human immunodeficiency virus) activity is described. Two structurally related compounds, 1, 3,3-(4-N-methyl-1,2,5,6-tetrahydropyridylmethyl)-1- phenyl-2-indolinone, and 2, its 4-N-methylpiperidinylmethyl analogue (Fig. 1), formed the basis of a structure-activity study. The synthesis of approximately 50 analogues and their respective activities vs. HIV are presented. Both 1 and 2 were effective inhibitors of HIV(IIIb) in cell protection assays with IC₉₀ values of 4.4 and 14.9μM (2.2 and 7.9μg ml⁻¹), respectively. In the same concentration range, 1 and 2 also inhibit syncytia formation. These compounds represent a novel class of anti-HIV agents which appear to act by inhibiting virus-dependent cell fusion.