Synthesis of extended uridine phosphonates derived from an allosteric P2Y2 receptor ligand

Lijun Song; Martijn D P Risseeuw; Izet Karalic; Matthew O Barrett; Kyle A Brown; T Kendall Harden; Serge Van Calenbergh

doi:10.3390/molecules19044313

Synthesis of extended uridine phosphonates derived from an allosteric P2Y2 receptor ligand

Molecules. 2014 Apr 4;19(4):4313-25. doi: 10.3390/molecules19044313.

Authors

Lijun Song¹, Martijn D P Risseeuw², Izet Karalic³, Matthew O Barrett⁴, Kyle A Brown⁵, T Kendall Harden⁶, Serge Van Calenbergh⁷

Affiliations

¹ Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. lijun.song@ugent.be.
² Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. martijn.risseeuw@ugent.be.
³ Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. izet.karalic@ugent.be.
⁴ Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7365, USA. matthew_barrett@med.unc.edu.
⁵ Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7365, USA. kyle_brown@med.unc.edu.
⁶ Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7365, USA. kendall_harden@med.unc.edu.
⁷ Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. serge.vancalenbergh@ugent.be.

Abstract

In this study we report the synthesis of C5/C6-fused uridine phosphonates that are structurally related to earlier reported allosteric P2Y2 receptor ligands. A silyl-Hilbert-Johnson reaction of six quinazoline-2,4-(1H,3H)-dione-like base moieties with a suitable ribofuranosephosphonate afforded the desired analogues after full deprotection. In contrast to the parent 5-(4-fluoropheny)uridine phosphonate, the present extended-base uridine phosphonates essentially failed to modulate the P2Y2 receptor.

MeSH terms

Allosteric Regulation
Astrocytes / cytology
Astrocytes / drug effects
Astrocytes / metabolism
Cell Line, Tumor
Humans
Ligands
Organophosphonates / chemical synthesis*
Organophosphonates / pharmacology
Purinergic P2Y Receptor Agonists / chemical synthesis*
Purinergic P2Y Receptor Agonists / pharmacology
Quinazolines / chemistry
Receptors, Purinergic P2Y2 / metabolism*
Uridine / analogs & derivatives
Uridine / chemical synthesis*
Uridine / pharmacology

Substances

Ligands
Organophosphonates
Purinergic P2Y Receptor Agonists
Quinazolines
Receptors, Purinergic P2Y2
Uridine