Synthesis, biological evaluation and structural determination of beta-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors.
Inhibitors of dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes. A series of beta-aminoacyl-containing cyclic hydrazine derivatives were synthesized and evaluated as DPP-IV inhibitors. One member of this series, (R)-3-amino-1-(2-benzoyl-1,2-diazepan-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one (10f), showed potent in vitro activity, good selectivity and in vivo efficacy in mouse models. Also, the binding mode of compound 10f was determined by X-ray crystallography.
Ahn
Jin Hee
JH
Bioorganic Science Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon 305-600, Republic of Korea. jhahn@krict.re.kr
Shin
Mi Sik
MS
Jun
Mi Ae
MA
Jung
Sun Ho
SH
Kang
Seung Kyu
SK
Kim
Kwang Rok
KR
Rhee
Sang Dal
SD
Kang
Nam Sook
NS
Kim
Sun Young
SY
Sohn
Sang-Kwon
SK
Kim
Sung Gyu
SG
Jin
Mi Sun
MS
Lee
Jie Oh
JO
Cheon
Hyae Gyeong
HG
Kim
Sung Soo
SS
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray; D054873:Dipeptidyl-Peptidase IV Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D008968:Molecular Conformation; D017434:Protein Structure, Tertiary
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D006834:Hydrazines; C029424:hydrazine; D052216:Glucagon-Like Peptide 1