(4-Piperidinyl)-piperazine: a new platform for acetyl-CoA carboxylase inhibitors.
Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the synthesis and structure-activity relationships of a series of disubstituted (4-piperidinyl)-piperazine derivatives as a new platform for ACC1/2 non-selective inhibitors.
Chonan
Tomomichi
T
Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co, Ltd, Saitama-shi, Saitama 331-9530, Japan. tomomichi.chonan@po.rd.taisho.co.jp
Oi
Takahiro
T
Yamamoto
Daisuke
D
Yashiro
Miyoko
M
Wakasugi
Daisuke
D
Tanaka
Hiroaki
H
Ohoka-Sugita
Ayumi
A
Io
Fusayo
F
Koretsune
Hiroko
H
Hiratate
Akira
A
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D010879:Piperazines; D010880:Piperidines; D000103:Acetyl-CoA Carboxylase