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Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists.

Publication ,  Journal Article
Guay, D; Beaulieu, C; Belley, M; Crane, SN; DeLuca, J; Gareau, Y; Hamel, M; Henault, M; Hyjazie, H; Kargman, S; Chan, CC; Xu, L; Gordon, R ...
Published in: Bioorganic & medicinal chemistry letters
May 2011

A weak antagonist of the pyrimidinergic receptor P2Y(14) 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 P2Y(14) antagonist with good oral bioavailability and provided sufficient exposure in mice to be used as a tool for future in vivo studies.

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Published In

Bioorganic & medicinal chemistry letters

DOI

EISSN

1464-3405

ISSN

0960-894X

Publication Date

May 2011

Volume

21

Issue

10

Start / End Page

2832 / 2835

Related Subject Headings

  • Structure-Activity Relationship
  • Receptors, Purinergic P2Y
  • Receptors, Purinergic P2
  • Pyrimidines
  • Purinergic P2 Receptor Antagonists
  • Pan troglodytes
  • Molecular Structure
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Biological Availability
 

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Guay, D., Beaulieu, C., Belley, M., Crane, S. N., DeLuca, J., Gareau, Y., … Black, W. C. (2011). Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists. Bioorganic & Medicinal Chemistry Letters, 21(10), 2832–2835. https://doi.org/10.1016/j.bmcl.2011.03.084
Guay, Daniel, Christian Beaulieu, Michel Belley, Sheldon N. Crane, Jeancarlo DeLuca, Yves Gareau, Martine Hamel, et al. “Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists.Bioorganic & Medicinal Chemistry Letters 21, no. 10 (May 2011): 2832–35. https://doi.org/10.1016/j.bmcl.2011.03.084.
Guay D, Beaulieu C, Belley M, Crane SN, DeLuca J, Gareau Y, et al. Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists. Bioorganic & medicinal chemistry letters. 2011 May;21(10):2832–5.
Guay, Daniel, et al. “Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists.Bioorganic & Medicinal Chemistry Letters, vol. 21, no. 10, May 2011, pp. 2832–35. Epmc, doi:10.1016/j.bmcl.2011.03.084.
Guay D, Beaulieu C, Belley M, Crane SN, DeLuca J, Gareau Y, Hamel M, Henault M, Hyjazie H, Kargman S, Chan CC, Xu L, Gordon R, Li L, Mamane Y, Morin N, Mancini J, Thérien M, Tranmer G, Truong VL, Wang Z, Black WC. Synthesis and SAR of pyrimidine-based, non-nucleotide P2Y14 receptor antagonists. Bioorganic & medicinal chemistry letters. 2011 May;21(10):2832–2835.
Journal cover image

Published In

Bioorganic & medicinal chemistry letters

DOI

EISSN

1464-3405

ISSN

0960-894X

Publication Date

May 2011

Volume

21

Issue

10

Start / End Page

2832 / 2835

Related Subject Headings

  • Structure-Activity Relationship
  • Receptors, Purinergic P2Y
  • Receptors, Purinergic P2
  • Pyrimidines
  • Purinergic P2 Receptor Antagonists
  • Pan troglodytes
  • Molecular Structure
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Biological Availability