Lack of human immunodeficiency virus‑1 integrase inhibitory activity of novel 3a, 4, 7, 7a‑tetrahydro‑1H‑isoindole‑1,3 (2H)‑dione derivatives

Abstract

Background: Majority of reported integrase (IN) inhibitors had an important
structural feature, i.e., 1,3‑diketo functional group. It plays a vital role in IN
inhibition by the formation of chelating triod with Mg+2 ions. Materials and
Methods: A novel series of fifteen 3‑(1,3‑dioxo‑3a, 4‑dihydro‑1H‑isoindol‑2
(3H,7H,7aH)‑yl)‑N‑(substituted phenyl) propanamide 4(a‑o) analogs were synthesized
by reacting the corresponding 3‑chloro‑N‑(substituted phenyl) propanamides 2(a‑o)
with 3a, 4,7,7a‑tetrahydro‑1H‑isoindole‑1,3 (2H)‑dione (3) in acetonitrile medium
in the presence of potassium carbonate. Various substituted 3‑chloro‑N‑(substituted
phenyl) propanamides 2(a‑o) were synthesized by treating appropriate substituted
anilines 1(a‑o) with 3‑chloro propionyl chloride in dichloromethane as solvent in the
presence of triethylamine as base. The synthesized compounds have been characterized
on the basis of fourier transform infrared spectrophotometerproton nuclear magnetic
resonance spectrophotometer,1
H NMR, Mass spectral and Elemental Analysis. Results:
All the synthesized compounds were evaluated for their human immunodeficiency
virus (HIV)‑1 INinhibitory activity. However, unlike other anti‑IN agents, none of
these molecules showed inhibition of either 3' processing, and strand transfer reactions
of HIV‑1 IN.