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Synthesis of (benzimidazol-2-yl)aniline derivatives as glycogen phosphorylase inhibitors
Affiliation:1. Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt;2. Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, Athens GR-11635, Greece;3. Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2—Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France;4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt;1. H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;2. Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D.E., Malaysia;3. Faculty of Applied Science, Universiti Teknologi MARA, Shah Alam 40450, Selangor D.E., Malaysia;4. PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan;5. Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, Pakistan;1. Laboratoire de Synthèse et Biocatalyse Organique, Département de Chimie, Faculté des Sciences, Université Badji Mokhtar Annaba, BP 12, 23000 Annaba, Algeria;2. Département de Physique et Chimie, Ecole Normale Supérieure d’Enseignement Technologique de Skikda, Cité des frères Boucetta, Azzaba, Skikda, Algeria;1. Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan;2. Laboratory of Epigenetics, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan;3. CREST, Japan Agency for Medical Research and Development (AMED), 1-7-1 Otemachi, Chiyoda-ku, Tokyo 100-0004, Japan;1. School of Chemistry, UNSW Australia, NSW 2052, Australia;2. Solid State & Elemental Analysis Unit, Mark Wainwright Analytical Centre, Division of Research, UNSW Australia, NSW 2052, Australia
Abstract:A series of (benzimidazol-2-yl)-aniline (1) derivatives has been synthesized and evaluated as glycogen phosphorylase (GP) inhibitors. Kinetics studies revealed that compounds displaying a lateral heterocyclic residue with several heteroatoms (series 3 and 5) exhibited modest inhibitory properties with IC50 values in the 400–600 μM range. Arylsulfonyl derivatives 7 (Ar: phenyl) and 9 (Ar: o-nitrophenyl) of 1 exhibited the highest activity (series 2) among the studied compounds (IC50 324 μM and 357 μM, respectively) with stronger effect than the p-tolyl analogue 8.
Keywords:Benzimidazole  Heterocycles  Glycogen phosphorylase  Enzyme inhibition
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