DESIGN AND NOVEL SYNTHESIS OF IMIDAZOAZINES AS PUTATIVE DRUG CANDIDATES

Abstract

A facile synthesis of2-unsubstituted-3-aminoimidazo[l, 2-a] heterocycles has been developed, by covalently linking glyoxylic acid on the solid support. This covalently linked Glyoxylic acid can be a useful preposition from a synthesis standpoint. This simple yet elegant protocol presents the first example of a formaldehyde equivalent covalently immobilized on the normal silica surface to carry out regio-selective Groebke-Blackburn-Bienaymé (GBB) reaction. The presence of a solid support facilitates the reaction to proceed without a solvent under microwave irradiation in good yields. Furthermore, 3 -aminoim idazo-azines molecules were docked against three well-validated malaria receptors Pf-dihydrofolate Reductase (DHFR). Pf-enoyl acyl carrier protein (ACP) reductase (ENR) and P1- protein kinase 7 (PK-7) receptors. An in-house library of 70 representative 3- aminoimidazo-azines was built and screened against well-established anti-malarial targets using molecular docking. In order to further analyse the reliability of our theoretically designed -. scaffolds with experimentally established inhibitors, for verification, 3D-QSAR accomplished studies of the top scorers from Docking studies. CoMFA/CoMSIA models were derived from a -. set of experimentally known Pf-DHFR inhibitors. The statistics demonstrated their reliability and appropriate predictive capability, especially the CoMSIA model. Six potent 3-aminoimidazoazines which were identified by molecular docking, also mapped well into CoMFA/CoMSIA contours with suitable inhibitory profile. Therefore, this comprehensive virtual approach presented new liits' as multi-target drugs efficiently, thereby increasing the likelihood of successful therapies