4-Substituted-7-N-alkyl-N-acetyl 2-aminobenzothiazole amides: Drug-like and non-xanthine based A2B adenosine receptor antagonists
| Autor: | Rachid Hamid, Roger David Norcross, Mary Lou Gubler, Ramakanth Sarabu, Fariborz Firooznia, Adrian Wai-Hing Cheung, John A. Brinkman, Nicholas Marcopulos, Lida Qi, Kevin Richard Guertin, Alexander Flohr, Jenny Tan, Gwendolyn Ramsey, Joseph Grimsby, Yang Wen |
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| Rok vydání: | 2010 |
| Předmět: |
Bicyclic molecule
Stereochemistry Organic Chemistry Clinical Biochemistry Pharmaceutical Science Receptor Adenosine A2B Xanthine Biochemistry Adenosine receptor Adenosine A2 Receptor Antagonists Structure-Activity Relationship chemistry.chemical_compound Adenosine A1 receptor chemistry Drug Discovery Molecular Medicine Potency Benzothiazoles Receptor Selectivity Molecular Biology G protein-coupled receptor |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 20:4140-4146 |
| ISSN: | 0960-894X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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