2-Amino-N-pyrimidin-4-ylacetamides as A2A receptor antagonists: 1. Structure-activity relationships and optimization of heterocyclic substituents
| Autor: | Silvia Gual, Chun Yang, Yang Sai, Kayvon Jalali, Sandra M. Lechner, Marion Lanier, Mark Santos, Yongsheng Chen, Maria Prat, Julio C. Castro-Palomino, John Saunders, Stacy Markison, John P. Williams, Emily Lin, Jaimie K. Rueter, Jose-Luis Diaz, María I. Crespo, Zhiyang Zuo, Manisha Moorjani, Deborah H. Slee, Raymond S. Gross, Xiaohu Zhang, Siobhan Malany |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.drug_class
Stereochemistry Drug Evaluation Preclinical Carboxamide Stereoisomerism Chemical synthesis chemistry.chemical_compound Structure-Activity Relationship Furan Drug Discovery Acetamides medicine Moiety Structure–activity relationship Animals Humans Thiazole Binding Sites Molecular Structure Adenosine A2 Receptor Antagonists Rats Pyrimidines chemistry Cyclization Hepatocytes Microsomes Liver Molecular Medicine Selectivity |
| Zdroj: | Journal of medicinal chemistry. 51(6) |
| ISSN: | 0022-2623 |
| Popis: | Previously we have described a novel series of potent and selective A2A receptor antagonists (e.g., 1) with excellent aqueous solubility.(1) While these compounds are efficacious A2A antagonists in vivo, the presence of an unsubstituted furyl moiety was a cause of some concern. In order to avoid the potential metabolic liabilities that could arise from an unsubstituted furyl moiety, an optimization effort was undertaken with the aim of replacing the unsubstituted furan with a more metabolically stable group while maintaining potency and selectivity. Herein, we describe the synthesis and SAR of a range of novel heterocyclic systems and the successful identification of a replacement for the unsubstituted furan moiety with a methylfuran or thiazole moiety while maintaining potency and selectivity. |
| Databáze: | OpenAIRE |
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