RSS-Feed abonnieren
DOI: 10.1055/s-0034-1371890
Microwave Assisted Synthesis and Anti-Lipase Activity of Some New Fluorine-Containing Benzimidazoles
Publikationsverlauf
received 08. Januar 2014
accepted 07. März 2014
Publikationsdatum:
02. April 2014 (online)
Abstract
In this study, a new series of fluorine containing benzimidazoles (4a–l) and bisbenzimidazoles (6a–c, 8) were synthesized by the reaction of o-phenylenediamines with iminoester hydrochlorides (3a–l, 7) in methanol under microwave irradiation. The structures of these newly synthesized compounds were identified by IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analysis data. The synthesized compounds were screened for their pancreatic lipase activities. Our results indicate that the compounds 6a, 6b and 6c can serve as an anti-lipase agent. The compounds 6b and 6c inhibited pancreatic lipase activity by 84.03% and 97.49% at a concentration of 3 µg/mL, respectively.
-
References
- 1 Velik J, Baliharova V, Fink-Gremmels J et al. Benzimidazole drugs and modulation of biotransformation enzymes. Res Vet Sci 2004; 76: 95-108
- 2 Kahveci B, Yilmaz F, Menteşe E et al. Microwave-Assisted Synthesis of Some Novel Benzimidazole Derivatives Containing Imine Function and Evaluation of Their Antimicrobial Activity. J Heterocycl Chem 2014; DOI: 10.1002/jhet.1593.
- 3 Demirayak S, Kayagil I, Yurttas L et al. Microwave Supported Synthesis of Some Novel 1,3-Diarylpyrazino[1,2-A]Benzimidazole Derivatives and Investigation of Their Anticancer Activities. Eur J Med Chem 2011; 46: 411-416
- 4 Kumar BVS, Vaidya SD, Kumar RV et al. Synthesis and Anti-bacterial Activity of Some Novel 2-(6-fluorochroman-2-yl)-1-alkyl/acyl/aroyl-1H-benzimidazoles. Eur J Med Chem 2006; 41: 599-604
- 5 Filler R, Saha R. Fluorine in medicinal chemistry: a century of progress and a 60-year retrospective of selected highlights. Future Med Chem 2009; 1: 777-791
- 6 Rudyuk VV, Fedyuk DV, Yagupolskii LM et al. N-Polyfluoroethyl and N-2-chlorodifluorovinyl Derivatives of Azoles. J Fluorine Chem 2004; 125: 1465-1471
- 7 Levine S, Deo R, Mahadevan KA et al. A comparative trial of a new antidepressant, fluoxetine. Br J Psychiatry 1987; 150: 653-655
- 8 Roth BD, Ortwine DF, Hoefle ML et al. Effects of Structural Modifications at the 2-and 5- positions of the pyrrole nucleus. J Med Chem 1990; 33: 21-31
- 9 Matsumoto J, Miyamoto T, Minamida A et al. Pyridonecarboxylic Acids as Antibacterial Agents. 2. Synthesis and Structure-activity Relationships of 1, 6,7-trisubstituted 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids, Including Enoxacin, a New Antibacterial Agent. J Med Chem 1984; 27: 292-301
- 10 Kim D, Kowalchick JE, Edmondson SD et al. Triazolopiperazine-amides as dipeptidyl peptidase IV inhibitors: Close analogs of JANUVIA™ (sitagliptin phosphate). Bioorg Med Chem Lett 2007; 17: 3373-3377
- 11 Liang W, Liu G. Synthesis of Mono- and Di-fluorinated Benzimidazoles. Chin J Chem 2011; 29: 983-990
- 12 Jeschke P. The Unique Role of Fluorine in the Design of Active Ingredients for Modern Crop Protection. Chem Bio Chem 2004; 5: 570-589
- 13 Isanbor C, O’Hagan D. Fluorine in medicinal chemistry: A review of anti-cancer agents. J Fluorine Chem 2006; 127: 303-313
- 14 Vasilyeva TP, Karimova NM, Slavich YV et al. Synthesis of Fluorine-containing Benzimidazole Derivatives. Russ Chem Bull 2010; 59: 186-191
- 15 Hao JY, Ge ZY, Yang SY et al. Convenient Synthesis of 2-Arylbenzimidazoles and 2,2’-Diaryl-bisbenzimidazoles. Synt Commun 2003; 33: 79-86
- 16 Zhang ZH, Li JJ, Gao YZ et al. Synthesis of 2-Substitued Benzimidazoles by Iodine-mediated Condensation of Orthoesters with 1,2-Phenylenediamines. J Heterocyclic Chem 2007; 44: 1509-1512
- 17 Wang ZX, Qin HL. Reaction of 1,3-Dicarbonyl Compounds with o-Phenylenediamine of 3,3’-Diaminobenzidine in water or Under Solvent-free Conditions via Microwave Irradiation. J Heterocyclic Chem 2005; 42: 1001-1005
- 18 Menteşe E, Bektaş H, Ülker S et al. Microwave-assisted synthesis of new benzimidazole derivatives with lipase inhibition activity. J Enzym Inhib Med Chem 2014; 29: 64-68
- 19 Kahveci B, Menteşe E, Özil M et al. An Efficient Synthesis of Benzimidazoles via a Microwave Technique and Evaluation of Their Biological Activities. Monatsh Chem 2013; 144: 993-1001
- 20 Menteşe E, Karaali N, Yılmaz F et al. Microwave-Assisted Synthesis and Biological Evaluation of Some Benzimidazole Derivatives Containing a 1,2,4-Triazole Ring. Archiv der Pharmazie 2013; 346: 556-561
- 21 Grivas S, Olsson K. An Improved Synthesis of 3,8-dimethyl-3H-imidazo[4,5-f]quinoxalin-2-amine (“MeIQx”) and its 2-14C-labelled analogue. Acta Chem Scand B 1985; B39: 31-34
- 22 Kurihara H, Asami S, Shibata H et al. Hypolipemic Effect of Cyclocaryapaliurus(Batal) Iljinskaja in Lipid-Loaded Mice. Biol Pharm Bull 2003; 26: 383-385
- 23 Jandacek RJ, Woods SC. Pharmaceutical approaches to the treatment of obesity. Drug Discov Today 2004; 15: 874-880
- 24 Pinner A. Die imidoether und ihre derivative, 1. Auflage Oppenheim; Berlin: 1982
- 25 Birari RB, Bhutani KK. Pancreatic lipase inhibitors from natural sources: unexplored potential. Drug Discov Today 2007; 12: 879-889
- 26 Weigle DS. Pharmacological Therapy of Obesity: Past, Present, and Future. J Clin Endocrinol Metab 2003; 88: 2462-2469