title: Synthesis, biological evaluation and structural determination of beta-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors.
abstract: 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.
authors.affiliation: Bioorganic Science Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon 305-600, Republic of Korea. jhahn@krict.re.kr
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Ahn
authors.forename: Mi Sik
authors.initials: MS
authors.lastname: Shin
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Jun
authors.forename: Sun Ho
authors.initials: SH
authors.lastname: Jung
authors.forename: Seung Kyu
authors.initials: SK
authors.lastname: Kang
authors.forename: Kwang Rok
authors.initials: KR
authors.lastname: Kim
authors.forename: Sang Dal
authors.initials: SD
authors.lastname: Rhee
authors.forename: Nam Sook
authors.initials: NS
authors.lastname: Kang
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sang-Kwon
authors.initials: SK
authors.lastname: Sohn
authors.forename: Sung Gyu
authors.initials: SG
authors.lastname: Kim
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Jin
authors.forename: Jie Oh
authors.initials: JO
authors.lastname: Lee
authors.forename: Hyae Gyeong
authors.initials: HG
authors.lastname: Cheon
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: 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
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D004791:Enzyme Inhibitors; D006834:Hydrazines; C029424:hydrazine; D052216:Glucagon-Like Peptide 1