A. Ahmed, Louise N. Dawe, M. Daneshtalab
2012
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0
Influential Citations
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Journal
Heterocycles
Abstract
The first synthesis of a series of 4-oxo-1,4-dihydrobenzo[h][1,3]thiazeto[3,2-a]quinoline carboxylic acids and their esters via oxidative cyclization of ethyl 2-((2-ethoxy-2-oxoethyl)thio)-4-hydroxybenzo[h]quinoline-3-carboxylate derivatives in the presence of a vicinal dihaloalkane, KI, and K2CO3 is described. Structures of the synthesized compounds were characterized by spectrometric and X-ray crystallographic analyses. INTRODUCTION 4-Oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives (quinolones) have dominated the antibacterial market for decades. Quinolones have a unique mechanism of action, they inhibit DNA synthesis by promoting cleavage of bacterial DNA in the DNA-enzyme complexes of DNA gyrase (main target in Gram-negative bacteria) and type IV topoisomerase (main target in Gram-positive bacteria), resulting in rapid bacterial death. Inhibitory activity of quinolones against human topoisomerase-2 has been reported by Kyowa-Hakko researchers via introduction of a series of tricyclic thiazoloquinolones that exhibited impressive anticancer activity. In continuation of our ongoing research towards the discovery of novel polycyclic quinoline-based antineoplastic agents using conventional synthetic procedures, we were able to isolate and identify, unexpectedly, a 4-oxo-benzo[h]thiazetoquinoline derivative (4a). The structure of this novel molecule was elucidated by H-NMR, C-NMR, HR-MS, and X-ray crystallography. Despite the availability of HETEROCYCLES, Vol. 85, No. 1, 2012 123