Synthesis and evaluation of piperidine urea derivatives as efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitors in diabetic ob/ob mice

Liming Zhang; Junhua Chen; Mengmeng Ning; Qingan Zou; Ying Leng; Jianhua Shen

doi:10.1016/j.bmcl.2012.02.095

Synthesis and evaluation of piperidine urea derivatives as efficacious 11β-hydroxysteroid dehydrogenase type 1 inhibitors in diabetic ob/ob mice

Bioorg Med Chem Lett. 2012 Apr 15;22(8):2748-52. doi: 10.1016/j.bmcl.2012.02.095. Epub 2012 Mar 3.

Authors

Liming Zhang¹, Junhua Chen, Mengmeng Ning, Qingan Zou, Ying Leng, Jianhua Shen

Affiliation

¹ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

PMID: 22440625
DOI: 10.1016/j.bmcl.2012.02.095

Abstract

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has attracted considerable attention as a potential target for the treatment of diabetes and metabolic syndrome. Herein we report the design, synthesis and efficacy evaluation of novel amide and urea 11β-HSD1 inhibitors. Structure-activity relationship studies led to the identification of 10c, which was efficacious in a diabetic ob/ob mouse model and reduced fasting and non-fasting blood glucose levels after ip dosing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
Animals
Diabetes Mellitus, Type 2
Enzyme Activation / drug effects
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Humans
Inhibitory Concentration 50
Mice
Mice, Obese
Molecular Structure
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology*
Structure-Activity Relationship
Urea / chemical synthesis*
Urea / chemistry
Urea / pharmacology

Substances

Enzyme Inhibitors
Piperidines
Urea
11-beta-Hydroxysteroid Dehydrogenase Type 1