2,3-Diarylthiophenes as selective EP1 receptor antagonists
| Autor: | Richard Friesen, Gillian Greig, Nicole Sawyer, Bernard Cote, Stacia Kargman, Sonia Lamontagne, Kathleen M. Metters, Richard Frenette, Yves Ducharme, Gary P. O'Neill, François Nantel, Marie-Claude Carrière, Evelyn Martins, Anne Chateauneuf, Danielle Denis, Marc Blouin |
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| Rok vydání: | 2005 |
| Předmět: |
Clinical Biochemistry
Pharmaceutical Science Thiophenes Pharmacology Biochemistry Chemical synthesis Cell Line Structure-Activity Relationship Pharmacokinetics In vivo Drug Discovery Animals Humans Receptors Prostaglandin E Structure–activity relationship Tissue Distribution Receptor Molecular Biology Chemistry Organic Chemistry Antagonist Brain Receptors Prostaglandin E EP1 Subtype In vitro Rats Cell culture Molecular Medicine Half-Life |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 15:1155-1160 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2004.12.005 |
| Popis: | The synthesis and the EP(1) receptor binding affinity of 2,3-diarylthiophene derivatives are described. The evaluation of the structure-activity relationship (SAR) in this series led to the identification of compounds 4, 7, and 12a, which exhibit high affinity for the human EP(1) receptor and a selectivity greater than 100-fold against the EP(2), EP(3), EP(4), DP, FP, and IP receptors and greater than 25-fold versus the TP receptor. These three antagonists present good pharmacokinetics in rats and significant differences in the way they are distributed in the brain. |
| Databáze: | OpenAIRE |
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