β-Lactam synthon-interceded diastereoselective synthesis of functionalized octahydroindole-based molecular scaffolds and their in vitro cytotoxic evaluation
European Journal of Medicinal Chemistry
Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India; Department of Chemistry, Punjab Technical University, Kapurthala 144601, India; Division of Medical Biochemistry, University of Cape Town, Anzio Road, Observatory 7925, South Africa; Department of Chemistry, Oklahoma State University, Stillwater, OK 74078, United States
A convenient and unprecedented synthesis of functionally enriched octahydroindole-based scaffolds has been developed via inter- and intra-molecular amidolysis of C-3 functionalized β-lactams. The cytotoxic evaluation on oesophageal cancer cell line WHCO1 has revealed 7d as the most potent of the test compounds exhibiting an IC50 value of 12.97 μM. The developed strategy further assumes significance as it entails the preparation of highly functionalized indoles without the aid of transition metal catalysis or pre-functionalization of substrates. © 2012 Elsevier Masson SAS. All rights reserved.
1 ( 4 chlorophenyl) 7 iodo 2 ( 4 methoxyphenyl)octahydroindole 3,4 dicarboxylic acid dimethyl ester; 1 ( 4 chlorophenyl) 7 iodo 2 phenyloctahydroindole 3,4 dicarboxylic acid dimethyl ester; 1,2 bis( 4 chlorophenyl) 7 iodooctahydroindole 3,4 dicarboxylic acid dimethyl ester; 2 ( 4 chlorophenyl) 7 iodo 1 phenyloctahydroindole 3,4 dicarboxylic acid dimethyl ester; 7 iodo 1,2 diphenyloctahydroindole 3,4 dicarboxylic acid dimethyl ester; 7 iodo 2 ( 4 methoxyphenyl) 1 phenyloctahydroindole 3,4 dicarboxylic acid dimethyl ester; 7 iodo 2 ( 4 methoxyphenyl) 1,4 tolyloctahydroindole 3,4 dicarboxylic acid dimethyl ester; 7 iodo 2 phenyl 1,4 tolyloctahydroindole 3,4 dicarboxylic acid dimethyl ester; antineoplastic agent; beta lactam derivative; indole derivative; metal; molecular scaffold; octahydroindole; octahydropyrrolo[4,3,2 de]isoquinoline 3,5 dione; synthon; unclassified drug; antineoplastic activity; article; cancer cell culture; catalysis; controlled study; cytotoxicity; diastereoisomer; drug potency; esophagus cancer; human; human cell; IC 50; in vitro study; one pot synthesis; phase transition; stereochemistry; Antineoplastic Agents; beta-Lactams; Cell Line, Tumor; Cell Proliferation; Crystallography, X-Ray; Dose-Response Relationship, Drug; Humans; Indoles; Models, Molecular; Molecular Conformation; Stereoisomerism; Structure-Activity Relationship