title: Novel trans-2-aryl-cyclopropylamine analogues as potent and selective dipeptidyl peptidase IV inhibitors.
abstract: A series of trans-2-aryl-cyclopropylamine derived compounds were synthesized and evaluated their biological activities against DPP-IV. The structure-activity relationships (SAR) led to the discovery of novel series of DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely related enzymes, DPP8, DPP-II and FAP. The studies identified a potent and selective DPP-IV inhibitor 24b, which exhibited the ability to both significantly inhibit plasma DPP-IV activity in rats and improve glucose tolerance in lean mice and diet induced obese mice.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Town, Miaoli Country 350, Taiwan, ROC.
authors.forename: Ting-Yueh
authors.initials: TY
authors.lastname: Tsai
authors.forename: Tsu
authors.initials: T
authors.lastname: Hsu
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.forename: Jai-Hong
authors.initials: JH
authors.lastname: Cheng
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Chung-Nien
authors.initials: CN
authors.lastname: Chang
authors.forename: Kai-Chia
authors.initials: KC
authors.lastname: Yeh
authors.forename: Su-Huei
authors.initials: SH
authors.lastname: Hsieh
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chien
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Chang
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Huang
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Chen-Lung
authors.initials: CL
authors.lastname: Huang
authors.forename: Ssu-Hui
authors.initials: SH
authors.lastname: Wu
authors.forename: Min-Hsien
authors.initials: MH
authors.lastname: Wang
authors.forename: Cheng-Tai
authors.initials: CT
authors.lastname: Lu
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Weir-Torn
authors.initials: WT
authors.lastname: Jiaang
mesh_terms: D000818:Animals; D003521:Cyclopropanes / Q000737:chemistry* / Q000494:pharmacology*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005951:Glucose Tolerance Test; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D003521:Cyclopropanes; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011480:Protease Inhibitors; C067351:cyclopropylamine; D018819:Dipeptidyl Peptidase 4