title: Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors.
abstract: A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Seoul 100-715, Republic of Korea.
authors.forename: Kyeong
authors.initials: K
authors.lastname: Lee
authors.forename: Ja-Il
authors.initials: JI
authors.lastname: Goo
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Minkyoung
authors.initials: M
authors.lastname: Kim
authors.forename: Shanthaveerappa K
authors.initials: SK
authors.lastname: Boovanahalli
authors.forename: Hye Ran
authors.initials: HR
authors.lastname: Park
authors.forename: Mun-Ock
authors.initials: MO
authors.lastname: Kim
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Lee
authors.forename: Yongseok
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D008862:Microsomes, Liver / Q000201:enzymology; D015394:Molecular Structure; D009765:Obesity / Q000188:drug therapy*; D051381:Rats; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D014280:Triglycerides; C031000:benzimidazole; C494883:Dgat1 protein, rat; D051048:Diacylglycerol O-Acyltransferase