2. Academic Validation
  3. Novel 5-nitropyrimidine derivatives bearing endo-azabicyclic alcohols/amines as potent GPR119 agonists

Novel 5-nitropyrimidine derivatives bearing endo-azabicyclic alcohols/amines as potent GPR119 agonists

  • Bioorg Med Chem. 2017 Jan 1;25(1):254-260. doi: 10.1016/j.bmc.2016.10.030.
Yuanying Fang 1,  Zunhua Yang 1,  Shankariah Gundeti 2,  Jongkook Lee 2,  Haeil Park 3
Affiliations

Affiliations

  • 1 College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
  • 2 College of Pharmacy of Kangwon National University, Chuncheon 200-701, Republic of Korea.
  • 3 College of Pharmacy of Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address: haeilp@kangwon.ac.kr.
PMID: 27825553 DOI: 10.1016/j.bmc.2016.10.030
Abstract

A series of GPR119 agonists based on a 5-nitropyrimidine scaffold bearing endo-azabicyclic substituents were synthesized and evaluated for their GPR119 agonistic activities. Most compounds exhibited much stronger EC50 values than that of oleoylethanolamide (OEA). Among them, derivatives from endo-azabicyclic alcohols displayed more potent GPR119 agonistic activities than compounds with endo-azabicyclic amines. Especially the optimized compounds (6, 7, 8, 12, 17) were shown to have potent biological activities and were identified as full agonists. Isopropyl carbamate compound 8 synthesized from endo-azabicyclic alcohol was observed to have the best EC50 value (0.6nM). Generally 2-fluoro substitution of the aryl group at the C4 position of 5-nitropyrimidine scaffold resulted in the increase of biological activity.

Keywords

5-Nitropyrimidine; Full agonists; GPR119 agonists; endo-Azabicyclic alcohol.

Figures