Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: Oxadiazolyl ketones

Compound 18h showed excellent inhibitory activity against DPPIV, good selectivity over DPPII and DPPVIII, and showed good PK, PD profile. Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure–activity relationships are discussed. Compo...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2007-08, Vol.17 (15), p.4167-4172
Main Authors: Koo, Ki Dong, Kim, Min Jung, Kim, Sungsub, Kim, Kyoung-Hee, Hong, Sang Yong, Hur, Gwong-Cheung, Yim, Hyeon Joo, Kim, Geun Tae, Han, Hee Oon, Kwon, O Hwan, Kwon, Tae Sik, Koh, Jong Sung, Lee, Chang-Seok
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Crystallography, X-Ray
Dipeptidyl Peptidase 4 - metabolism
Dipeptidyl-Peptidase IV Inhibitors
Dogs
DPPIV inhibitors
General and cellular metabolism. Vitamins
Haplorhini
Ketones - chemical synthesis
Ketones - chemistry
Ketones - pharmacology
Kinetics
Medical sciences
Models, Molecular
Molecular Structure
Oxadiazolyl ketones
Pharmacology. Drug treatments
Protease Inhibitors - chemical synthesis
Protease Inhibitors - chemistry
Protease Inhibitors - pharmacology
Rats
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Compound 18h showed excellent inhibitory activity against DPPIV, good selectivity over DPPII and DPPVIII, and showed good PK, PD profile. Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure–activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2007.05.046