Computer Assisted Design Synthesis and Biological Evaluation of Some Novel Heterocyclic Compounds

Abstract

This thesis deals with the investigations carried out by the writer on computer assisted design, synthesis and biological evaluation of some novel heterocyclic compounds. The first chapter of the thesis deals with an introduction to drug discovery, diabetes mellitus and its management/treatment, in addition to lead optimisation pathway for thiazolidinediones, peroxisome proliferator-activated receptors, computer assisted drug design and PPAR-y as a target and a review of literature. The second chapter of the thesis deals with the scope and objectives of the present study. In particular, it explains the need for undertaking the present study on design, synthesis and biological evaluation of some novel heterocyclic compounds belonging to the class of glitazones. The third chapter of the thesis deals with the CADD techniques used such as 2D QSAR, 3D QSAR, docking, synthesis, characterisation and biological evaluation of some thiazolidine-2,4-diones and their bioisostere 2-thioxo-thiazolidine-4-ones incorporated with pyridine and furan. The fourth chapter gives the results obtained in the present study in the form of tables and figures including a detailed discussion on the results obtained. The following are the some of the some of the major findings of the present investigation. 1. The developed 2D QSAR model reveals that properties such as partition coefficient, polarity, polarisability, volume, number of nitrogen and oxygen atoms in relation to their charges and the molecular shape of the molecule are to be considered apart from triglyceride lowering activity (experimental parameter), while designing newer thioglitazones, with potential antihyperglycemic activity. 2. 3D QSAR models, CoMFA and CoMSIA, reveal that thiazolidinedione ring system connected to the benzylidene ring system followed by a two carbon linker and a hydrophobic tail is the basic requirement for thiazolidinedione class of compounds to exhibit antinyperglycemic activity. Dockings studies validate the findings of the 3D QSAR study.