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

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.