Synthesis of (benzimidazol-2-yl)aniline derivatives as glycogen phosphorylase inhibitors.
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 IC50values in the 400-600μM range. Arylsulfonyl derivatives 7 (Ar: phenyl) and 9 (Ar: o-nitrophenyl) of 1 exhibited the highest activity (series 2) among the studied compounds (IC50324μM and 357μM, respectively) with stronger effect than the p-tolyl analogue 8.
Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt. Electronic address: sh12galal@hotmail.com.
Shadia A
SA
Galal
Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt.
Muhammad
M
Khattab
Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, Athens GR-11635, Greece.
Fotini
F
Andreadaki
Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, Athens GR-11635, Greece. Electronic address: echrysina@eie.gr.
Evangelia D
ED
Chrysina
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. Electronic address: jean-pierre.praly@univ-lyon1.fr.
Jean-Pierre
JP
Praly
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Fatma A F
FAF
Ragab
Department of Chemistry of Natural and Microbial Products, Division of Pharmaceutical and Drug Industries, National Research Centre, Dokki, 12622 Cairo, Egypt.
Hoda I
HI
El Diwani
D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011817:Rabbits; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D024981:Glycogen Phosphorylase
Benzimidazole; Enzyme inhibition; Glycogen phosphorylase; Heterocycles