title: Design and synthesis of a new class of malonyl-CoA decarboxylase inhibitors with anti-obesity and anti-diabetic activities.
abstract: A new series of thiazole-substituted 1,1,1,3,3,3-hexafluoro-2-propanols were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Key analogs caused dose-dependent decreases in food intake and body weight in obese mice. Acute treatment with these compounds also led to a drop in elevated blood glucose in a murine model of type II diabetes.
authors.affiliation: Department of Medicinal Chemistry, Metabolic Disorders, Drug Metabolism and Pharmacology, Merck Research Laboratories, Rahway, NJ 07065, USA. haifeng_tang@merck.com
authors.forename: Haifeng
authors.initials: H
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.forename: Reynalda K
authors.initials: RK
authors.lastname: de Jesus
authors.forename: Lihu
authors.initials: L
authors.lastname: Yang
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Levorse
authors.forename: Karen A
authors.initials: KA
authors.lastname: Owens
authors.forename: Taro E
authors.initials: TE
authors.lastname: Akiyama
authors.forename: Raynald
authors.initials: R
authors.lastname: Bergeron
authors.forename: Gino A
authors.initials: GA
authors.lastname: Castriota
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Doebber
authors.forename: Kenneth P
authors.initials: KP
authors.lastname: Ellsworth
authors.forename: Michael E
authors.initials: ME
authors.lastname: Lassman
authors.forename: Cai
authors.initials: C
authors.lastname: Li
authors.forename: Margaret S
authors.initials: MS
authors.lastname: Wu
authors.forename: Bei B
authors.initials: BB
authors.lastname: Zhang
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Chapman
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Alexander
authors.initials: A
authors.lastname: Pasternak
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D015195:Drug Design; D004435:Eating / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy*; D020005:Propanols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006845:Hydrocarbons, Fluorinated
chemical_list: D019440:Anti-Obesity Agents; D001786:Blood Glucose; D002262:Carboxy-Lyases; D007004:Hypoglycemic Agents; D020005:Propanols; D013844:Thiazoles; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated; C021532:malonyl-CoA decarboxylase