Discovery and structure-activity relationships of piperidinone- and piperidine-constrained phenethylamines as novel, potent, and selective dipeptidyl peptidase IV inhibitors
| Autor: | Xiaofeng Li, Thomas W. von Geldern, Kenton L. Longenecker, James M. Trevillyan, Chunqiu Lai, Kent D. Stewart, Bradley J. Backes, Thomas H. Lubben, Daisy Pireh, Anita J Kempf-Grote, Hing L. Sham, Zhonghua Pei, David W A Beno, Stephen J. Ballaron |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Dipeptidyl Peptidase 4
Molecular Conformation Biological Availability Phenethylamines Peptide Crystallography X-Ray Dipeptidyl peptidase Structure-Activity Relationship Piperidines Drug Discovery Adenosine Deaminase Inhibitors Structure–activity relationship Glucose homeostasis Animals Humans Dipeptidyl peptidase-4 Piperidones Glycoproteins chemistry.chemical_classification Dipeptidyl-Peptidase IV Inhibitors biology Chemistry Stereoisomerism Rats Enzyme Biochemistry Enzyme inhibitor biology.protein Molecular Medicine |
| Zdroj: | Journal of medicinal chemistry. 50(8) |
| ISSN: | 0022-2623 |
| Popis: | Dipeptidyl peptidase IV (DPP4) inhibitors are emerging as a new class of therapeutic agents for the treatment of type 2 diabetes. They exert their beneficial effects by increasing the levels of active glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are two important incretins for glucose homeostasis. Starting from a high-throughput screening hit, we were able to identify a series of piperidinone- and piperidine-constrained phenethylamines as novel DPP4 inhibitors. Optimized compounds are potent, selective, and have good pharmacokinetic profiles. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|