Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration

A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and identified as long-acting DPP-IV inhibitors. The mode of binding and the effect on the plasma glucose level were evaluated. A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhi...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2007-04, Vol.15 (7), p.2631-2650
Main Authors: Kondo, Takashi, Nekado, Takahiro, Sugimoto, Isamu, Ochi, Kenya, Takai, Shigeyuki, Kinoshita, Atsushi, Tajima, Yohei, Yamamoto, Susumu, Kawabata, Kazuhito, Nakai, Hisao, Toda, Masaaki
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Chromatography, Thin Layer
Dipeptidyl Peptidase 4 - blood
Dipeptidyl-Peptidase IV Inhibitors
Dogs
DPP-IV inhibitor
General and cellular metabolism. Vitamins
Glucose Tolerance Test
Humans
Indicators and Reagents
Macaca fascicularis
Magnetic Resonance Spectroscopy
Male
Medical sciences
Oxidation-Reduction
Pharmacology. Drug treatments
Prolyl-2-cyanopyrrolidine
Protease Inhibitors - chemical synthesis
Protease Inhibitors - pharmacology
Pyrrolidines - chemical synthesis
Pyrrolidines - pharmacology
Rats
Rats, Sprague-Dawley
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Summary:A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and identified as long-acting DPP-IV inhibitors. The mode of binding and the effect on the plasma glucose level were evaluated. A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure–activity relationships are also presented.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2007.01.041