Synthesis of extended uridine phosphonates derived from an allosteric P2Y2 receptor ligand.
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.
Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. lijun.song@ugent.be.
Lijun
L
Song
Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. martijn.risseeuw@ugent.be.
Martijn D P
MD
Risseeuw
Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. izet.karalic@ugent.be.
Izet
I
Karalic
Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7365, USA. matthew_barrett@med.unc.edu.
Matthew O
MO
Barrett
Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7365, USA. kyle_brown@med.unc.edu.
Kyle A
KA
Brown
Department of Pharmacology, University of North Carolina, School of Medicine, Chapel Hill, NC 27599-7365, USA. kendall_harden@med.unc.edu.
T Kendall
TK
Harden
Laboratory for Medicinal Chemistry, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium. serge.vancalenbergh@ugent.be.
Serge
S
Van Calenbergh
D000494:Allosteric Regulation; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology; D058912:Purinergic P2Y Receptor Agonists / Q000138:chemical synthesis* / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry; D058473:Receptors, Purinergic P2Y2 / Q000378:metabolism*; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology
D008024:Ligands; D063065:Organophosphonates; D058912:Purinergic P2Y Receptor Agonists; D011799:Quinazolines; D058473:Receptors, Purinergic P2Y2; D014529:Uridine