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Synthesis of Privileged Scaffolds by Using Diversity‐Oriented Synthesis
Author(s) -
Surakanti Ramu,
Sanivarapu Sumalatha,
Thulluri Chiranjeevi,
Iyer Pravin S.,
Tangirala Raghuram S.,
Gundla Rambabu,
Addepally Uma,
Murthy Y. L. N.,
Velide Lakshmi,
Sen Subhabrata
Publication year - 2013
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201201203
Subject(s) - combinatorial chemistry , reagent , alkylation , chemistry , in silico , lactam , broad spectrum , combinatorial synthesis , stereochemistry , organic chemistry , catalysis , biochemistry , gene
An elegant reagent‐controlled strategy has been developed for the generation of a diverse range of biologically active scaffolds from a chiral bicyclic lactam. Reduction of the chiral lactam with LAH or alkylation with LHMDS to trigger different cyclization reactions have been shown to generate privileged scaffolds, such as pyrrolidines, indolines, and cyclotryptamines. Their amenability to substitution allows us to create various compound libraries by using these scaffolds. In silico studies were used to estimate the drug‐like properties of these compounds. Selected compounds were subjected to anticancer screening by using three different cell lines. In addition, all these compounds were subjected to antibacterial screening to gauge the spectrum of biological activity that was conferred by our DOS methodology. Gratifyingly, with no additional iterative cycles, our method directly generated anticancer compounds with potency at low nanomolar concentrations, as represented by spiroindoline 14 .