title: Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration.
abstract: A series of 5beta-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure-activity relationships are also presented.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co. Ltd., 3-1-1 Sakurai, Shimamoto, Mishima, Osaka 618-8585, Japan. t.kondou@ono.co.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nekado
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugimoto
authors.forename: Kenya
authors.initials: K
authors.lastname: Ochi
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Takai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tajima
authors.forename: Susumu
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Kawabata
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D000818:Animals; D002855:Chromatography, Thin Layer; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004285:Dogs; D005951:Glucose Tolerance Test; D006801:Humans; D007202:Indicators and Reagents; D008252:Macaca fascicularis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007202:Indicators and Reagents; D011480:Protease Inhibitors; D011759:Pyrrolidines; D018819:Dipeptidyl Peptidase 4