title: Chemical synthesis, biological evaluation and structure-activity relationship analysis of azaisoindolinones, a novel class of direct enoyl-ACP reductase inhibitors as potential antimycobacterial agents.
abstract: 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.
authors.affiliation: Laboratoire de Chimie de Coordination du CNRS, 205, Route de Narbonne, F-31077 Toulouse, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Deraeve
authors.forename: Ioana Miruna
authors.initials: IM
authors.lastname: Dorobantu
authors.forename: Farah
authors.initials: F
authors.lastname: Rebbah
authors.forename: Frédéric
authors.initials: F
authors.lastname: Le Quéméner
authors.forename: Patricia
authors.initials: P
authors.lastname: Constant
authors.forename: Annaïk
authors.initials: A
authors.lastname: Quémard
authors.forename: Vania
authors.initials: V
authors.lastname: Bernardes-Génisson
authors.forename: Jean
authors.initials: J
authors.lastname: Bernadou
authors.forename: Geneviève
authors.initials: G
authors.lastname: Pratviel
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D010088:Oxidoreductases; C085257:InhA protein, Mycobacterium