Previously we described a significant tuberculostatic activity of 2-phenylalkyl- and 2-cyclohexylalkylbenzimidazoles [1]. The designated minimum concentration inhibiting the growth of M. tuberculosis strains (MIC) in vitro was at the level appropriate for applied chemotherapeutics. We found that tested compounds were more active against resistant than sensitive strains and the presence of cyclohexylethyl substituent at position C-2 of the benzimidazole system was important for their activity.

These findings prompted us to extend our studies on the development of novel tuberculostatic agents, here we disclose the synthesis of novel 2-(2-cyclohexylethyl)-1H-benzo[d]imidazoles. We synthesized structures in which the cyclohexylethyl group is connected to the benzimidazole system or systems of benzimidazole type structure. Target compounds were obtained by the heating of 3-cyclohexylpropanoic acid with respective diamines according to the method described by Algul and co-workers [2] and based on the use of polyphosphoric acid (PPA) as a solvent with strong acidic properties (method A).

Promising results of biological studies encouraged us to undertake the synthesis of other benzimidazole type compounds 2-6. Imidazopyridines 2 and 4 were obtained by the heating of 3-cyclohexylpropanoic acid and appropriate diamine in a diglyme (di(2-dimethoxyethyl) ether) solution (method B). Due to the liquid form of 2-(2-cyclohexylethyl)-3H-imidazo[4,5-c]pyridine the compound 4 was synthesized as dihydrochloride.

All the newly synthesized compounds were characterized by IR and ¹H NMR spectra as well as the elemental analysis.  They have been also screened for their tuberculostatic, antibacterial and cytotoxic activities.

This study is supported by the National Science Centre, Cracow (grant no. 2011/01/B/NZ4/01187).

References:

[1] H. Foks, D. Pancechowska-Ksepko, W. Kuźmierkiewicz, Z. Zwolska, E. Augustynowicz-Kopeć, M. Janowiec Chem. Heterocyc. Compd. 2006, 42, 611.

[2] O. Algul, A. Kaessler, Y. Apcin, A. Yilmaz, J. Jose Molecules 2008, 13, 736.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/25368 must be provided.

1. Novel 2-(2-phenalkyl)-1H-benzo[d]imidazoles: synthesis, characteristics, tuberculostatic and cytotoxic activities
2. Novel N-substituted 2-(2-phenalkyl)-1H-benzo[d]imidazoles: synthesis, characteristics and tuberculostatic activity
3. Synthesis and antifungal activity of novel S-esters and S,S'-diesters of N'-(2-hydroxybenzoyl) hydrazinecarbo- dithioic acids
4. Synthesis and tuberculostatic activity of new N’-(6-methoxypyrazine-2-carbonyl)dithiocarbazic acid esters and their amidrazone analogs
5. Formation of 4-Pyridone-3-carboxamide-1-β-D-ribonucleoside triphosphate in the Erythrocytes, Endothelium and Cardiomyocytes and its Effect on ATP Concentration
6. THE IMPORTANCE OF THE TYPE OF ISONIAZID ACETYLATION IN MONITORING OF TUBERCULOSIS TREATMENT.
7. SYNTHESIS AND ANTITUBERCULOUS ACTIVITY OF NEW 3,5-DISUBSTITUTED- 1,2,4-OXADIAZOLES
8. NEW 3-ALKENYL DERIVATIVES OF RIFAMYCIN ANTIBIOTICS