Synthesis and biological evaluation of pyrazoline analogues with beta-amino acyl group as dipeptidyl peptidase IV inhibitors

  • Eur J Med Chem. 2008 Sep;43(9):1889-902. doi: 10.1016/j.ejmech.2007.11.029.
Mi Ae Jun  1 ,  Woul Seong Park ,  Seung Kyu Kang ,  Ki Young Kim ,  Kwang Rok Kim ,  Sang Dal Rhee ,  Myung Ae Bae ,  Nam Sook Kang ,  Sang-Kwon Sohn ,  Sung Gyu Kim ,  Jie Oh Lee ,  Duck Hyung Lee ,  Hyae Gyeong Cheon ,  Sung Soo Kim ,  Jin Hee Ahn
Affiliations
  • 1. Drug Discovery Division, Korea Research Institute of Chemical Technology, Yuseong-Gu, Daejeon 305-600, Republic of Korea.
PMID: 18243422 DOI: 10.1016/j.ejmech.2007.11.029
Abstract

A series of pyrazoline derivatives with beta-amino acyl group were synthesized and evaluated for their ability to inhibit Dipeptidyl Peptidase IV. Several pyrazoline derivatives exhibited submicromolar inhibitory activities against DPP-IV. X-ray co-crystal structure of initial hit compound 1h was determined. Among this series, carboxylic acid substituted pyrazoline derivative 2u was the most active and greatly decreased the inhibitory activity toward CYP3A4 enzyme.