4-Substituted-7-N-alkyl-N-acetyl 2-aminobenzothiazole amides: drug-like and non-xanthine based A2B adenosine receptor antagonists.

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Cheung AW, Brinkman J, Firooznia F, Flohr A, Grimsby J, Gubler ML, Guertin K, Hamid R, Marcopulos N, Norcross RD, Qi L, Ramsey G, Tan J, Wen Y, Sarabu R

4-Substituted-7-N-alkyl-N-acetyl 2-aminobenzothiazole amides: drug-like and non-xanthine based A2B adenosine receptor antagonists.

Bioorg Med Chem Lett. 2010 Jul 15;20(14):4140-6. doi: 10.1016/j.bmcl.2010.05.056. Epub 2010 May 20.

PubMed ID

20541935 [ View in PubMed

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Abstract

7-N-Acetamide-4-methoxy-2-aminobenzothiazole 4-fluorobenzamide (compound 1) was chosen as a drug-like and non-xanthine based starting point for the discovery of A(2B) receptor antagonists because of its slight selectivity against A(1) and A(2A) receptors and modest A(2B) potency. SAR exploration of compound 1 described herein included modifications to the 7-N-acetamide group, substitution of the 4-methoxy group by halogens as well as replacement of the p-flouro-benzamide side chain. This work culminated in the identification of compound 37 with excellent A(2B) potency, modest selectivity versus A(2A) and A(1) receptors, and good rodent PK properties.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Adenosine	Adenosine receptor A1	EC 50 (nM)	310	N/A	N/A	Details
Adenosine	Adenosine receptor A2a	EC 50 (nM)	700	N/A	N/A	Details
Adenosine	Adenosine receptor A2b	EC 50 (nM)	24000	N/A	N/A	Details
Adenosine	Adenosine receptor A3	EC 50 (nM)	290	N/A	N/A	Details