Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: oxadiazolyl ketones.
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.
Koo
Ki Dong
KD
LG Life Sciences, Ltd/R&D Park, 104-1 Munji-dong, Yuseong-gu, Daejeon 305-380, Republic of Korea.
Kim
Min Jung
MJ
Kim
Sungsub
S
Kim
Kyoung-Hee
KH
Hong
Sang Yong
SY
Hur
Gwong-Cheung
GC
Yim
Hyeon Joo
HJ
Kim
Geun Tae
GT
Han
Hee Oon
HO
Kwon
O Hwan
OH
Kwon
Tae Sik
TS
Koh
Jong Sung
JS
Lee
Chang-Seok
CS
D000818:Animals; D018360:Crystallography, X-Ray; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D000882:Haplorhini; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007659:Ketones; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4