Pharmacophore-based design of sphingosine 1-phosphate-3 receptor antagonists that include a 3,4-dialkoxybenzophenone scaffold
| Autor: | Takeshi Hasegawa, Tomoyuki Sada, Atsuko Sakurai, Hiroshi Takasugi, Kazuhiro Uemoto, Yuuki Koide, Akira Murakami, and Atsuo Takahashi, Atsushi Nishida, Naoki Mochizuki |
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| Rok vydání: | 2007 |
| Předmět: |
Models
Molecular Databases Factual medicine.drug_class Molecular Conformation Quantitative Structure-Activity Relationship CHO Cells Transfection chemistry.chemical_compound Benzophenones Cricetulus Cricetinae Drug Discovery medicine Animals Humans Database search engine Sphingosine-1-phosphate Receptor G protein-coupled receptor Sphingosine Chemistry Stereoisomerism Receptor antagonist Receptors Lysosphingolipid Biochemistry Drug Design Molecular Medicine Calcium Pharmacophore Signal transduction |
| Zdroj: | Journal of medicinal chemistry. 50(3) |
| ISSN: | 0022-2623 |
| Popis: | Sphingosine 1-phosphate (S1P) receptors are G-protein-coupled receptors. Among the five identified subtypes S1P1-5, the S1P3 receptor expressed on vascular endothelial cells has been shown to play an important role in cell proliferation, migration, and inflammation. A pharmacophore-based database search was used to identify a potent scaffold for an S1P3 receptor antagonist by common feature-based alignment and further validated using the Guner-Henry (GH) scoring method. Assumed excluded volumes were merged into this model to evaluate the steric effect with the S1P3 receptor. Three commercially available compounds were identified as S1P3 receptor antagonists, with IC50 values |
| Databáze: | OpenAIRE |
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