Design, synthesis, and progress toward optimization of potent small molecule antagonists of CC chemokine receptor 8 (CCR8)
| Autor: | Gregory J. LaRosa, Kenneth G. Carson, Chuang Lu, Roland Kolbeck, Shomir Ghosh, Sean Smith, Daniel Flynn, Priya Eddy, Tracy J. Jenkins, Geraldine C Harriman, Cheng Zhang, Jianping Guo, Hua Yang, Robert A. Horlick, Ukti Mani, Michael A. Patane, Bing Guan, Bruce Jaffee, Robert Bennett, Elder Amy M, Vinita Uttamsingh, Shannon Chi, Qing Ye |
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| Rok vydání: | 2006 |
| Předmět: |
Pyrrolidines
hERG CCL1 CCR8 Ether Receptors CCR8 Cell Line Structure-Activity Relationship Piperidines Drug Discovery Structure–activity relationship Humans Amination biology Molecular Structure Chemistry Chemotaxis Ligand (biochemistry) Small molecule Biochemistry Drug Design biology.protein Molecular Medicine Receptors Chemokine CC chemokine receptors |
| Zdroj: | Journal of medicinal chemistry. 49(9) |
| ISSN: | 0022-2623 |
| Popis: | Activation of CCR8 by its ligand CCL1 may play an important role in diseases such as asthma, multiple sclerosis, and cancer. The study of small molecule CCR8 antagonists will help establish the validation of these hypotheses. We report the design, synthesis, and progress toward optimization of potent small molecule CCR8 antagonists identified from a high-throughput screen. These analogues exhibit good potency in binding and chemotaxis assays, show good selectivity versus the hERG channel, and have good eADME (early absorption, distribution, metabolism, and excretion) profiles. |
| Databáze: | OpenAIRE |
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