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

  • Yang, Zunhua
  • Fang, Yuanying
  • Pham, Tuan-Anh N.
  • Lee, Jongkook
  • Park, Haeil
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초록

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 EC50 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). (c) 2012 Elsevier Ltd. All rights reserved.

키워드

GPR119 agonistType 2 diabetes5-NitropyrimidinesAzabicyclic alcoholsAzabicyclic aminesPROTEIN-COUPLED RECEPTORDISCOVERYPOTENTINHIBITORSAGENTS
제목
Synthesis and biological evaluation of 5-nitropyrimidine analogs with azabicyclic substituents as GPR119 agonists
저자
Yang, ZunhuaFang, YuanyingPham, Tuan-Anh N.Lee, JongkookPark, Haeil
DOI
10.1016/j.bmcl.2012.12.011
발행일
2013-03-01
유형
Article
저널명
Bioorganic & Medicinal Chemistry Letters
23
5
페이지
1519 ~ 1521