Recent developments in selective agonists and antagonists acting at purine and pyrimidine receptors
- 1 November 1996
- journal article
- Published by Wiley in Drug Development Research
- Vol. 39 (3-4), 289-300
- https://doi.org/10.1002/(sici)1098-2299(199611/12)39:3/4<289::aid-ddr8>3.0.co;2-n
Abstract
The SAR at adenosine (P1) and ATP (P2) receptors is reviewed, with emphasis on recently developed selective agonists and antagonists. These include partial (e.g., N6-ethyl-8-cyclopentylaminoadenosine) and full A1 agonists (e.g., NNC 21-0136, 2-chloro-N6-[(R)-(benzothiazolylthio-2-propyl]adenosine), A2 antagonists (e.g., the non-xanthines: SCH58261, 5-amino-7-(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and ZM241385, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3a][1,3,5]triazinyl-amino]ethyl)-phenol; and the 1-propargyl-8-styrylxanthines), and A3 agonists (e.g., CI-IB-MECA, 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluron-amide). Novel adenosine receptor antagonists (e.g., BTH4, ethyl 3-benzylthio-4,5,6,7-tetrahydro-benzo[c]thiophen-4-one-1-carboxylate) have been discovered through screening libraries of natural products and heterocyclic derivatives. The first A3 selective antagonists to be identified include derivatives of flavones (MRS 1067), 1,4-dihydropyridines (MRS 1097), triazolonaphthyridine (L-249313), and thiazolopyrimidine (L-268605). Potent P2 receptor agonists are known. For example, 2-HexylthioAMP is a highly potent agonist at the yet uncloned P2Y receptor in C6 glioma cells. Suramin is a weak and non-selective P2 blocker, while a truncated derivative, NF023, appears to be selective for P2X receptors. More selective P2 antagonists are under development, with the cloning of these receptors. [35S]ATP-γS has been used as a radioligand for the direct labeling of several subtypes of cloned P2X receptors (P2X1-P2X4).Keywords
This publication has 60 references indexed in Scilit:
- A unifying purinergic hypothesis for the initiation of painThe Lancet, 1996
- Induction of Apoptosis in HL-60 Human Promyelocytic Leukemia Cells by Adenosine A3Receptor Agonists: Volume219,Number 3 (1996), pages 904–910Biochemical and Biophysical Research Communications, 1996
- Tetrahydrobenzothiophenone Derivatives as a Novel Class of Adenosine Receptor AntagonistsJournal of Medicinal Chemistry, 1996
- Survey of Nonxanthine Derivatives as Adenosine Receptor LigandsNucleosides and Nucleotides, 1996
- General pharmacology of SDZ WAG 994, a potent selective and orally active adenosine A1 receptor agonistDrug Development Research, 1995
- Novel competitive antagonists for P2 purinoceptorsEuropean Journal of Pharmacology: Molecular Pharmacology, 1994
- Structure activity relationships for derivatives of adenosine‐5′‐triphosphate as agonists at P2 purinoceptors: Heterogeneity within P2x and P2y subtypesDrug Development Research, 1994
- Adenosine A1 antagonists. 2. Structure-activity relationships on diuretic activities and protective effects against acute renal failureJournal of Medicinal Chemistry, 1992
- Selective A1-Antagonists for Treatment of Cognitive DeficitsNucleosides and Nucleotides, 1991
- N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine and its uronamide derivatives. Novel adenosine agonists with both high affinity and high selectivity for the adenosine A2 receptorJournal of Medicinal Chemistry, 1988