title: Synthesis and biological evaluation of tert-butyl-5-methylpyrimidin-piperazine derivatives as anti-obesity agents.
abstract: A series of tert-butyl-5-methylpyrimidin-piperazine derivatives were synthesized and their anti-obesity activities were evaluated. Compounds 4g and 5j were found to have significant effects in down-regulating the triglyceride level of 3T3-L1 adipocytes. 5j exhibited remarkable therapeutic effects on the diet-induced obesity (DIO) mouse model at 20 mg kg(-1)  day(-1) for 4 weeks by decreasing the weights of body, liver, and fat. 5j also regulated serum biomarkers to appropriate ranges, exerted therapeutic activity of steatosis in liver tissue and ameliorated the obese-related symptoms. In addition, 5j significantly decreased the blood glucose levels in oral glucose tolerance tests and improved the insulin sensitivity in insulin tolerance tests. These results suggest that 5j could be a candidate for obesity treatment.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical, Sichuan University, Chengdu, P. R. China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.forename: Yuzhi
authors.initials: Y
authors.lastname: Pu
authors.forename: Heying
authors.initials: H
authors.lastname: Pei
authors.forename: Linhong
authors.initials: L
authors.lastname: He
authors.forename: Suhong
authors.initials: S
authors.lastname: Fu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015195:Drug Design; D005234:Fatty Liver / Q000209:etiology / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
chemical_list: D019440:Anti-Obesity Agents; D015415:Biomarkers; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D007328:Insulin; D010879:Piperazines; D014280:Triglycerides
keywords: Diet-induced obesity; Dyslipidemia; OGTT; Serum biomarker; Triglycerides