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

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Scheiff AB, Yerande SG, El-Tayeb A, Li W, Inamdar GS, Vasu KK, Sudarsanam V, Muller CE

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

Bioorg Med Chem. 2010 Mar 15;18(6):2195-203. doi: 10.1016/j.bmc.2010.01.072. Epub 2010 Feb 4.

PubMed ID

20188574 [ View in PubMed

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Abstract

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 A(1)-selective antagonists. Acylation of the 2-amino group was found to be crucial for high A(1) affinity. The best compound of the present series was 2-benzoylamino-5-p-methylbenzoyl-4-phenylthiazole (16 m) showing a K(i) value of 4.83 nM at rat and 57.4 nM at human A(1) receptors combined with high selectivity versus the other AdoR subtypes. The compound behaved as an antagonist in GTP shift assays at A(1) receptors. Compound 16 m may serve as a new lead structure for the development of second-generation non-xanthine-derived A(1) antagonists which have potential as novel drugs.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Theophylline	Adenosine receptor A1	Ki (nM)	6770	N/A	N/A	Details
Theophylline	Adenosine receptor A2a	Ki (nM)	6700	N/A	N/A	Details
Theophylline	Adenosine receptor A2b	Ki (nM)	9070	N/A	N/A	Details