Heteroaryl substituted bis-trifluoromethyl carbinols as malonyl-CoA decarboxylase inhibitors.
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.
Cheng
Jie-Fei
JF
Department of Chemistry and Discovery Biology, Chugai Pharma LLC., 6275 Nancy Ridge Dr., San Diego, CA 92121, USA. jcheng@trlusa.com
Mak
Chi Ching
CC
Huang
Yujin
Y
Penuliar
Richard
R
Nishimoto
Masahiro
M
Zhang
Lin
L
Chen
Mi
M
Wallace
David
D
Arrhenius
Thomas
T
Chu
Donald
D
Yang
Guang
G
Barbosa
Miguel
M
Barr
Rick
R
Dyck
Jason R B
JR
Lopaschuk
Gary D
GD
Nadzan
Alex M
AM
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
D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D002262:Carboxy-Lyases; C021532:malonyl-CoA decarboxylase; D005947:Glucose; D000432:Methanol