898273-33-1Relevant academic research and scientific papers
Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group
Kondo, Takashi,Nekado, Takahiro,Sugimoto, Isamu,Ochi, Kenya,Takai, Shigeyuki,Kinoshita, Atsushi,Hatayama, Akira,Yamamoto, Susumu,Kishikawa, Katsuya,Nakai, Hisao,Toda, Masaaki
, p. 1613 - 1631 (2008/09/20)
A series of (4β-substituted)-l-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented.
