title: 3-[2-((2S)-2-cyano-pyrrolidin-1-yl)-2-oxo-ethylamino]-3-methyl-butyramide analogues as selective DPP-IV inhibitors for the treatment of type-II diabetes.
abstract: Based on the structures of NVP-DPP728 (1) and NVP-LAF237 (Vildagliptin, 2), three series of DPP-IV inhibitors were synthesized by linking substituted anilines, benzylamines, and phenylethylamines to (2S)-cyanopyrrolidine through a linker. More than 20 compounds were evaluated for their in vitro DPP-IV inhibition and selectivity profile over DPP-II, DPP8, and FAP enzymes. Selected compounds 5f and 7i showed in vivo plasma DPP-IV inhibition and inhibited glucose excursion in OGTT after oral administration in Wistar rats. Compound 5f (DPP-IV IC50 = 116 nM) has the potential for development as antidiabetic agent.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, No. 35, Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan, ROC.
authors.forename: Mohane Selvaraj
authors.initials: MS
authors.lastname: Coumar
authors.forename: Chung-Nien
authors.initials: CN
authors.lastname: Chang
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Chien
authors.forename: Ting-Yueh
authors.initials: TY
authors.lastname: Tsai
authors.forename: Jai-Hong
authors.initials: JH
authors.lastname: Cheng
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Wu
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Han
authors.forename: Ssu-Hui
authors.initials: SH
authors.lastname: Wu
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Huang
authors.forename: Tsu
authors.initials: T
authors.lastname: Hsu
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Hsu
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Weir-Torn
authors.initials: WT
authors.lastname: Jiaang
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives; D058892:Adenosine Deaminase Inhibitors; D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology*; D000814:Aniline Compounds; D000818:Animals; D001596:Benzylamines; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D009570:Nitriles; D010627:Phenethylamines; D011759:Pyrrolidines; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D000077597:Vildagliptin
chemical_list: C121834:1-(((2-((5-cyanopyridin-2-yl)amino)ethyl)amino)acetyl)-2-cyano-(S)-pyrrolidine; D058892:Adenosine Deaminase Inhibitors; D000577:Amides; D000814:Aniline Compounds; D001596:Benzylamines; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D009570:Nitriles; D010627:Phenethylamines; D011759:Pyrrolidines; C006866:butyramide; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane