title: Synthesis and biological evaluation of 5-nitropyrimidine analogs with azabicyclic substituents as GPR119 agonists.
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).
authors: College of Pharmacy of Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors: Zunhua
authors: Z
authors: Yang
authors: Yuanying
authors: Y
authors: Fang
authors: Tuan-Anh N
authors: TA
authors: Pham
authors: Jongkook
authors: J
authors: Lee
authors: Haeil
authors: H
authors: Park
mesh_terms: D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D006801:Humans; D008968:Molecular Conformation; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D053961:Azabicyclo Compounds; C519854:GPR119 protein, human; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled