- Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists
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A weak antagonist of the pyrimidinergic receptor P2Y14 containing a dihydropyridopyrimidine core was identified through high-throughput screening. Subsequent optimization led to potent, non-UTP competitive antagonists and represent the first reported non-nucleotide antagonists of this receptor. Compound 18q was identified as a 10 nM P2Y14 antagonist with good oral bioavailability and provided sufficient exposure in mice to be used as a tool for future in vivo studies.
- Guay, Daniel,Beaulieu, Christian,Belley, Michel,Crane, Sheldon N.,DeLuca, Jeancarlo,Gareau, Yves,Hamel, Martine,Henault, Martin,Hyjazie, Huda,Kargman, Stacia,Chan, Chi Chung,Xu, Lijing,Gordon, Robert,Li, Lianhai,Mamane, Yael,Morin, Nicolas,Mancini, Joseph,Thérien, Michel,Tranmer, Geoffrey,Truong, Vouy Linh,Wang, Zhaoyin,Black, W. Cameron
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scheme or table
p. 2832 - 2835
(2011/06/24)
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- SUBSTITUTED FUSED PYRIMIDINES AS ANTAGONISTS OF GPR105 ACTIVITY
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Fused pyrimidine compounds of structural formula (I) are effective as antagonists of the biological activity of the GPR105 protein. They are useful for the treatment, control or prevention of disorders responsive to antagonism of this receptor, such as diabetes, particularly, Type 2 diabetes, insulin resistance, hyperglycemia, lipid disorders, obesity, atherosclerosis, and Metabolic Syndrome.
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