2. Academic Validation
  3. 4-Substituted-7-N-alkyl-N-acetyl 2-aminobenzothiazole amides: drug-like and non-xanthine based A2B adenosine receptor antagonists

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.
Adrian Wai-Hing Cheung 1,  John Brinkman,  Fariborz Firooznia,  Alexander Flohr,  Joseph Grimsby,  Mary Lou Gubler,  Kevin Guertin,  Rachid Hamid,  Nicholas Marcopulos,  Roger D Norcross,  Lida Qi,  Gwendolyn Ramsey,  Jenny Tan,  Yang Wen,  Ramakanth Sarabu
Affiliations

Affiliation

  • 1 Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. [email protected]
PMID: 20541935 DOI: 10.1016/j.bmcl.2010.05.056
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.

Figures