A Bioisosteric and Scaffold Hopping Approach for the Design and Synthesis of Double Ring Replacement Analogues of 4‐Aryl‐4H‐Chromenes and in silico Tubulin Inhibitor Studies

Abstract

An eco‐friendly reaction protocol was developed for the synthesis of heterocyclic hybrid scaffolds through bioisosteric replacement and scaffold hopping approach. The isosteric analogues of salicylaldehyde were designed, identified/synthesized and employed in a three component reaction to afford bioisosteric analogues of 4‐aryl‐4H‐chromenes. Thus central core swapping of benzene‐pyridine/pyrazole ring on 4‐aryl‐4H‐chromenes was achieved under simple one‐pot reaction conditions and easy work‐up. Docking studies show that almost all the compounds possess good binding affinities at the colchicine binding site of tubulin.

Multicomponent synthesis of pyrrolo[2,1-a]isoindolylidene-malononitrile (PIYM) fluorophores and their photophysical properties

“…24–29 As a part of our research interests, our group is actively engaged in synthesizing hybrid building blocks to develop libraries of diverse bioactive small molecules through multicomponent reactions, incorporating the principles of diversity-oriented synthesis. 30–33…”

“…[24][25][26][27][28][29] As a part of our research interests, our group is actively engaged in synthesizing hybrid building blocks to develop libraries of diverse bioactive small molecules through multicomponent reactions, incorporating the principles of diversity-oriented synthesis. [30][31][32][33] Isoindoline derivatives are renowned for their chromophoric nature in several commercial dyes but are least exploited as fluorescent materials. [34][35][36][37][38][39][40] This might be due to the less available synthetic methodologies focused on improving the intramolecular charge transfer (ICT) of the isoindoline moiety with effectively extended conjugation.…”

Ethylenediamine Functionalized Cellulose Acetate [CAEDA] Nanosized Solid Base Catalyst in the Synthesis of 2‐Amino‐4H‐Chromenes and 5‐Substituted‐1H‐Tetrazoles

“…substituted 2-amino-4H-chromenes. [39][40][41][42][43][44][45][46][47][48][49][50][51][52] Very recent work has been done to synthesize Alkyl-4-(1H-indol-3 yl)-2-alkyl-4H-chromene-3-carboxylates using water extract of lemon [107] and is still in process but many of the protocols suffer from certain drawbacks such as tedious work-up, long reaction time, harsh reaction conditions etc. So, we present here the synthesis of 2amino-4H-chromenes using dimedone, different substituted aromatic aldehydes and malononitrile using ethanol as a solvent at 80°C in presence of Cellulose acetate [1,2-ethylenediamine][CAEDA] as a catalyst (Scheme 1).…”

Design and synthesis of benzothiazole/thiophene-4H-chromene hybrids

“…Our research group is actively engaged in developing multicomponent reaction protocols for accessing diverse scaffolds particularly 4-heterocycle-substituted-4H-chromene with inherent exibility for incorporating appendages including replacing the benzene ring of chromene moiety by heterocyclic ring, by innovative design and synthesis of building blocks. [28][29][30][31][32][33][34] Herein we disclose the design ( Fig. 1) and synthesis of hybrid heterocyclic's by simultaneous incorporation of substituent's at 3 and 4 positions of 4H-chromenes in an efficient three component reaction (Fig.…”