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...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2007-08, Vol.17 (15), p.4167-4172
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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
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Zusammenfassung:	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