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]
- 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