2-Amino-5-benzoyl-4-phenylthiazoles: Development of potent and selective adenosine A1 receptor antagonists

A series of 2-amino-5-benzoyl-4-phenylthiazole derivatives was investigated in radioligand binding studies at adenosine receptor (AdoR) subtypes with the goal to obtain potent and A1-selective antagonists. Acylation of the 2-amino group was found to be crucial for high A1 affinity. The best compound of the present series was 2-benzoylamino-5-p-methylbenzoyl-4-phenylthiazole (16m) showing a Ki value of 4.83 nM at rat and 57.4 nM at human A1 receptors combined with high selectivity versus the other AdoR subtypes. The compound behaved as an antagonist in GTP shift assays at A1 receptors. Compound 16m may serve as a new lead structure for the development of second-generation non-xanthine-derived A1 antagonists which have potential as novel drugs.

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