Synthesis and biological evaluation of 5-nitropyrimidine analogs with azabicyclic substituents as GPR119 agonists

  • Bioorg Med Chem Lett. 2013 Mar 1;23(5):1519-21. doi: 10.1016/j.bmcl.2012.12.011.
Zunhua Yang  1 ,  Yuanying Fang ,  Tuan-Anh N Pham ,  Jongkook Lee ,  Haeil Park
Affiliations
  • 1. College of Pharmacy of Kangwon National University, Chuncheon 200-701, Republic of Korea.
PMID: 23374864 DOI: 10.1016/j.bmcl.2012.12.011
Abstract

5-Nitropyrimidine analogs substituted with conformationally restricted azabicyclic amines and alcohols were prepared and evaluated their agonistic activity against human GPR119. The analogs bearing endo-azabicyclic amines and alcohols (7, 8, 11, and 12) exhibited full agonistic activities while the analogs with exo-azabicyclic amines and alcohols were proved as partial agonists (9, 10, 13, and 14) regardless of their EC(50) values. 5-Nitropyrimidine analogs with (2-fluoro-4-methylsulfonyl)phenylamino group (8, 10, 12, 14) showed more potent GPR119 activation activities than the analogs without fluorine in all cases (7, 9, 11, 13).