Synthesis of new antineoplastic agents based on imidazo[2,1- a ]pyridine
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Synthesis of new antineoplastic agents based on imidazo[2,1-a]pyridine Lyudmila M. Potikha1*, Volodymyr S. Brovarets2 1
Taras Shevchenko National University of Kyiv, 64 Volodymyrska St., Kyiv 01033, Ukraine; е-mail: [email protected] 2 V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, 1 Murmanska St., Kyiv 02094, Ukraine; е-mail: [email protected] Submitted June 6, 2020 Accepted June 29, 2020
Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(11), 1460–1464
2-Aryl-2-(2-aryl-2-oxoethyl)-1H,2H,3H-imidazo[1,2-a]pyridin-4-ium bromides were obtained in the reaction of (2Z)-4-bromo-1,3diphenylbut-2-en-1-one derivatives with 2-aminopyridines in benzene. The effect of the structure of the starting reagents on the results of the reactions was studied. Antitumor activity of 2-(4-chlorophenyl)-2-[2-(4-chlorophenyl)-2-oxoethyl]-1H,2H,3H-imidazo[1,2-a]pyridin4-ium bromide was determined, which showed high antitumor potential of the test compound on 60 human cancer cell lines. Keywords: 2-aminopyridine, γ-bromodipnone, imidazo[2,1-a]pyridine, antitumor activity, Michael addition.
In recent decades, imidazo[1,2-a]pyridine, a basic nitrogenous heterocycle, has taken leading positions in the design of biologically active compounds. Its derivatives exhibit various biological and pharmacological activity.1 The success of this structural fragment in pharmacology is evidenced by the list of drugs that have already found their place in the clinic, for example, the neurotropic drugs alpidem and zolpidem,2 cardiotonic olprinone,3 the neuroleptic mosapramine.4 A number of imidazo[1,2-a]pyridine derivatives have been used as leading molecules for the creation of anticancer drugs5,6 (Fig. 1), some of which are already undergoing clinical trials.5c This stimulates constant interest in the development of new synthetic methods for constructing the imidazo[1,2-a]pyridine system, and to date, various synthetic strategies and approaches have been proposed.7 Earlier,8 we found a method for constructing the imidazole fragment to azines based on the reaction of γ-bromodipnone with 2-aminopyridine and 2-aminopyrimidine. The method allows one to obtain partially hydrogenated derivatives. The antitumor activity of the representatives of this segment of imidazo[1,2-a]pyridine derivatives has also been studied in recent years,6 which prompted us to study the applicability of our 0009-3122/20/56(11)-1460©2020 Springer Science+Business Media, LLC
Figure 1. Antineoplastic agents based on imidazo[1,2-a]pyridine.
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Chemistry of Heterocyclic Compounds 2020, 56(11), 1460–1464
method for the synthesis of a series of compounds for further testing of their biological activity. In this work, the number of derivatives of γ-halogen-α,βunsaturated ketones and 2-aminopyridine was expanded. (2Z)-1,3-Diaryl-4-bromobut-2-en-1-one (γ-bromodipnone) derivatives 1a–d readily react with 2-aminopyridines 2a–d in PhH (Scheme 1). However, the resulting quaternary pyridinium salts 3 are unstable and, under the reaction conditions,
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