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

Authors :: Yang Z
Fang Y
Pham TA
Lee J
Park H
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2013 Mar 01; Vol. 23 (5), pp. 1519-21. Date of Electronic Publication: 2012 Dec 20.
Publication Year :: 2013
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).<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Subjects :: Azabicyclo Compounds chemistry
Diabetes Mellitus, Type 2 drug therapy
Humans
Molecular Conformation
Pyrimidines chemistry
Structure-Activity Relationship
Azabicyclo Compounds chemical synthesis
Azabicyclo Compounds pharmacology
Pyrimidines chemical synthesis
Pyrimidines pharmacology
Receptors, G-Protein-Coupled agonists

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