Synthesis and structure–activity relationship studies of tyrosine-based antagonists at the human P2X7 receptor
| Autor: | Wangzhong Chen, Kenneth A. Jacobson, Lak Shin Jeong, Bhalchandra V. Joshi, Yong-Chul Kim, Ga Eun Lee, Hyung Ryong Moon |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.drug_class
Stereochemistry Clinical Biochemistry Pharmaceutical Science Carboxamide Biochemistry Article Cell Line Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Purinergic P2 Receptor Antagonists medicine Humans Structure–activity relationship Moiety Tyrosine Receptor Molecular Biology Organic Chemistry Stereoisomerism Receptor antagonist Piperazine chemistry Molecular Medicine Receptors Purinergic P2X7 Ethidium bromide |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 18:571-575 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2007.11.077 |
| Popis: | Analogues of the P2X 7 receptor antagonist KN-62, modified at the piperazine and arylsulfonyl groups, were synthesized and assayed at the human P2X 7 receptor for inhibition of BzATP-induced effects, that is, uptake of a fluorescent dye (ethidium bromide) in stably transfected HEK293 cells and IL-1β release in differentiated THP-1 cells. Substitution of the arylsulfonyl moiety with a nitro group increased antagonistic potency relative to methyl substitution, such that compound 21 was slightly more potent than KN-62. Substitution with d -tyrosine in 36 and sterically bulky tyrosyl 3,5-dimethyl groups in 9 enhanced antagonistic potency. |
| Databáze: | OpenAIRE |
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