Nucleoside-derived antagonists

Fig. 7.16 LAN (Locked nucleic acid) nucleosides as conformationally constrained nucleoside-derived A3 AR antagonists...

Theophylline-9-6-D-glucopyranosyl 6 -monophosphate has been isolated from Cicer arietinum this is the first example of a naturally occurring theophylline nucleoside derivative. N -(2-hydroxy-ethyl) adenosine has been isolated from the mycelia of Cordyceps and Isaria fungi, and identified as a calcium antagonist and an 2... 

Gao Z-G, Kim S-K, Biadatti T, Chen W, Lee K, Barak D, Kim S-G, Johnson CR, Jacobson KA (2002) Structural determinants of A3 adenosine receptor activation nucleoside ligands at the agonist/antagonist boundary. J Med Chem 445 4471-4484 Gao Z-G, Blaustein JB, Gross AS, Melman N, Jacobson KA (2003) M -Substituted adenosine derivatives selectivity, efficacy, and species differences at A3 adenosine receptors. Biochem Pharmacol 65 1675-1684... 

Many 6-alkylaminopurine nucleosides are important adenosine receptor antagonists, and acyclic nucleotide analogues derived from 6-dialkylaminopurines are strong antivirals, anti-neoplastic agents, and immunomodulators. Recently, several 6-(arylalkynyl)-, 6-(arylalkenyl)-, and 6-(arylalkyl)purines have been reported to exhibit cytokinine activity. Suzuki crosscoupling reactions of 9-benzyl-6-chloropurine with boronic acids have recently been reported to provide 6-substituted purines in moderate to excellent yields (Eq. (46)) [77]. 

PURINE P2 RECEPTOR ANTAGONISTS P2 receptors (P2-purinoceptors) are quite distinct from PI receptors (see ADENOSINE RECEPTORS), with the former activated by nucleotides, typically ATP and the latter by nucleosides, typically adenosine see purine receptor agonists. As a result of coupling considerations and structural information derived from cloning and expression studies, the P2 purinoceptors are now divided into two main classes. 

A nitrogen mustard derivative of barbituric acid has been reported without antitumour data [206]. 5-Diazobarbituric anhydride (XLVI) has been found to be amoebicidal at 0-001 mg/ml vs. Endamoeba histolytica [207]. The inhibition is reversed by nucleotides, but not by the bases or nucleosides. It had previously been found that (XLVI) is a cytosine antagonist in the yeasts, Torula utilis and Saccharomyces cerevisiae Hansen [208]. This compound is prepared by the action of nitrous and nitric acids on 5-aminouracil-6-sulphonic acid [209], and as a cyclic derivative of a barbituric acid, it has quite different properties from the pyrimidinetriones. 

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