Synthesis of hybrid analogues of caffeine and eudistomin D and its affinity for adenosine receptors.

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Ishiyama H, Nakajima H, Nakata H, Kobayashi J

Synthesis of hybrid analogues of caffeine and eudistomin D and its affinity for adenosine receptors.

Bioorg Med Chem. 2009 Jul 1;17(13):4280-4. doi: 10.1016/j.bmc.2009.05.036. Epub 2009 May 18.

PubMed ID

19481943 [ View in PubMed

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Abstract

Four bis-N-n-propyl analogues (3-6) in the uracil ring of two hybrid molecules (1 and 2) of caffeine and eudistomin D, a beta-carboline alkaloid from a marine tunicate, were synthesized, and their affinity and selectivity for adenosine receptors A(1), A(2A), and A(3) were examined. All the compounds (3-6) showed better potency as adenosine receptor ligands than caffeine. Bis-N-n-propylation (3 and 4, respectively) of the uracil ring in 1 and 2 resulted in higher affinity for A(1) and A(2A) adenosine receptors. Furthermore, it was found that a compound (5) possessing a n-propyloxy group at C-7 in compound 3 with a nitrogen at the beta-position of the pyridine ring (beta-N type) enhanced remarkably affinity for adenosine receptor A(3) subtype, while n-propyloxy substitution (compound 6) at C-5 in compound 4 with a nitrogen at the delta-position of the pyridine ring (delta-N type) reduced affinity for all the adenosine receptor, A(1), A(2A), and A(3). Among all the compounds (1-6) examined, compound 5 showed the most potent affinity for adenosine receptor A(3) subtype (K(i) value, 0.00382 microM).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Caffeine	Adenosine receptor A1	Ki (nM)	49000	N/A	N/A	Details
Caffeine	Adenosine receptor A2a	Ki (nM)	18100	N/A	N/A	Details