title: Heteroaryl substituted bis-trifluoromethyl carbinols as malonyl-CoA decarboxylase inhibitors.
abstract: A series of heteroaryl-substituted bis-trifluoromethyl carbinols were prepared and evaluated as malonyl-CoA decarboxylase (MCD) inhibitors. Some thiazole-based derivatives showed potent in vitro MCD inhibitory activities and significantly increased glucose oxidation rates in isolated working rat hearts.
authors.affiliation: Department of Chemistry and Discovery Biology, Chugai Pharma LLC., 6275 Nancy Ridge Dr., San Diego, CA 92121, USA. jcheng@trlusa.com
authors.forename: Jie-Fei
authors.initials: JF
authors.lastname: Cheng
authors.forename: Chi Ching
authors.initials: CC
authors.lastname: Mak
authors.forename: Yujin
authors.initials: Y
authors.lastname: Huang
authors.forename: Richard
authors.initials: R
authors.lastname: Penuliar
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishimoto
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Mi
authors.initials: M
authors.lastname: Chen
authors.forename: David
authors.initials: D
authors.lastname: Wallace
authors.forename: Thomas
authors.initials: T
authors.lastname: Arrhenius
authors.forename: Donald
authors.initials: D
authors.lastname: Chu
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Miguel
authors.initials: M
authors.lastname: Barbosa
authors.forename: Rick
authors.initials: R
authors.lastname: Barr
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.forename: Gary D
authors.initials: GD
authors.lastname: Lopaschuk
authors.forename: Alex M
authors.initials: AM
authors.lastname: Nadzan
mesh_terms: D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000737:chemistry*; D066298:In Vitro Techniques; D000432:Methanol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D005947:Glucose; D000432:Methanol