Adenosine receptors ligands are currently being developed as promising agents for CNS disorders (Parkinson's, Alzheimer's, morbus, ischaemia) [1].

The lipophilicity is a parameter regarded as an important factor significantly influencing CNS bioavailability.

Searching for new selective ARs ligands, we have synthesized tricyclic derivatives with imidazo-, pyrimido- and diazepino annelated ring and N-cycloalkyl moiety.

The obtained compounds were bioassayed for the affinity towards adenosine A₁ and A_2A rat receptors in in vitro binding tests, showing A_2A selectivity.

In aim to evaluate the structure-bioactivity relationships, we determined their lipophilicity expressed by R_M0 values using planar RP-TLC method. The theoretical partition coefficient parameters (logP) were also calculated using computer programs: HyperChem, PALLAS, CAChe Project Leader, SciLogP for Alchemy [2]. The correlation between parameters of lipophilicity (R_M0, logP) and activity K_i was examined.

Supported in part by Polish State Committee for Scientific Research (Grant No 2P05F02226)

References:

[1]. S. Hess; Recent advances in adenosine receptor antagonist research. Expert. Opin. Ther. Patents 2001, 11, 1-29

[2] HyperChem 7.5 by Hypercube Inc., PALLAS 3.2.2.1 (demo version) by CompuDrug, CAChe Project Leader 6.1 by Fujitsu Ltd., SciLogP 3.0 for Alchemy (demo version) by SciVision

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