Literature

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.

DOI： 10.1016/j.bmcl.2010.05.056

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

Bioorganic & Medicinal Chemistry Letters 2010.0

Discovery of benzothiazole-based adenosine A2B receptor antagonists with improved A2A selectivity

Bioorganic & Medicinal Chemistry Letters 2011.0

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

Bioorganic & Medicinal Chemistry 2010.0

Novel 1,3-Disubstituted 8-(1-benzyl-1H-pyrazol-4-yl) Xanthines: High Affinity and Selective A2BAdenosine Receptor Antagonists

Journal of Medicinal Chemistry 2006.0

Discovery of Potent and Highly Selective A2BAdenosine Receptor Antagonist Chemotypes

Journal of Medicinal Chemistry 2016.0

Structure−Activity Relationships at Human and Rat A2B Adenosine Receptors of Xanthine Derivatives Substituted at the 1-, 3-, 7-, and 8-Positions