Chemical synthesis, biological evaluation and structure-activity relationship analysis of azaisoindolinones, a novel class of direct enoyl-ACP reductase inhibitors as potential antimycobacterial agents

The synthesis and biological evaluation of azaisoindolinone compounds embedding a lipophilic chain on the framework were performed. These compounds were designed as InhA inhibitors and as anti-Mycobacterium tuberculosis agents. Structure-activity relationships concerning the length and the location of the lipophilic chain around the azaisoindolinone framework, the suppression of the phenyl group, the bioisosteric substitution of ether link and alkylating of the tertiary hydroxyl and the hemiamidal nitrogen were also investigated, revealing insightful information and thereby enabling further diversification of the azaisoindolinone scaffold for new antitubercular agents. (C) 2011 Elsevier Ltd. All rights reserved.