Identification Optimization and biological evaluation of drug like heterocyclic templates for the treatment of type II diabetes mellitus

Abstract

newlineThe research work entitled Identification, Optimization and Biological Evaluation of Drug like Heterocyclic Templates for the Treatment of Type II Diabetes Mellitus is divided into eight chapters mentioned in brief as follows. newlineChapter 1 outlines historical aspects of diabetes, epidemiology, prevalence, classification and current therapies, limitations and emerging targets for management of Type 2 Diabetes Mellitus. newlineChapter 2 sketches about the role of G-Protein Coupled receptors as an important protein to be targeted against T2DM therapy. It also draws explains why targeting GPR40 has drawn considerable attention from both academia and industry as a novel target for the treatment of type 2 diabetes with minimal risk of hypoglycemia. newlineChapter 3 gives the idea about aim and objectives of the research strategy implemented, using various computational tools for the lead optimization of the drug like hetero cyclic templates. newlineChapter 4 describes about how 3D structures of the GPR40 receptor were constructed based on homology modeling principles. Exploring such study gives insights into the characterization of key H-bonding, hydrophobic residues, and defining the binding pocket of the receptor. newlineChapter 5 enlightens a common structural motif, identified in combiphore (Structure and Ligand based pharmacophore) for GPR40 modulation. Combiphore approach explores maximum structural information which can serve as a good lead to develop novel GPR40 modulators. newlineChapter 6 embraces 3D-QSAR techniques CoMFA, CoMSIA and HQSAR on the series 3-aryl- 3-ethoxypropanoic acids. Structural requirements for designing novel GPR40 modulators with improved activity can be achieved by designing the compounds based on their counter maps. Contour maps provides positive and negative contribution, favoured and disfavoured regions with R1 and R2 substitutions, gives hint for the modification required to design new molecules with improved biological activity. newlineIn chapter 7, synthesis of five different series namely, Pyrazole containi