Structure-activity relationships for N6-substituted adenosines at a brain A1-adenosine receptor with a comparison to an A2-adenosine receptor regulating coronary blood flow.

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摘要：

A series of 145 N 6-substituted adenosines have been screened as inhibitors of the binding of [ 3H]cyclohexyladenosine to an A 1-adenosine receptor in rat brain membranes and the results compared to the potencies of these analogs in increasing coronary blood flow via activation of an A 2-adenosine receptor. The A 1 receptor shows greater stereoselectivity in the N 6 region of the receptor towards asymmetric aralkyl substituents, and shows greater bulk tolerance in the N 6 region such that it retains affinity for certain N 6-tertiary alkyladenosines and N 6-cycloalkyladenosines that are inactive at the coronary A 2 receptor. At the A 1 receptor, the most potent analogs have either aliphatic N 6-substituents with four or more methylene residues or have an N 6-halophenyl substituent. At the A 2 receptor, the most potent analogs have an N 6-phenethyl or similar heteroarylethyl substituent. Certain sets or series of analogs appear useful for identifying the subtypes of adenosine receptors involved in physiological functions.

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DOI：

10.1016/0006-2952(86)90042-0

被引量：

385

年份：

1986