Discovery of Potent Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 3. Amide (C-Ring) Structure−Activity Relationship and Improvement of Overall Properties of Arylthio Cinnamides
| Autor: | Zhili Xin, Edward B. Reilly, Kennan C. Marsh, Yihong Li, Jeffery R. Huth, J.T. Link, and Peter DeVries, Nathan L. Lubbers, Zhonghua Pei, Sandra Leitza, Thomas W. von Geldern, Yi Gao, Bryan F. Cox, Greg Okasinski, Gang Liu |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Models Molecular Magnetic Resonance Spectroscopy Molecular model Intercellular Adhesion Molecule-1 Myocardial Infarction Nipecotic Acids Sulfides Cell Line Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Amide Drug Discovery Cell Adhesion Animals Structure–activity relationship Binding site Cell adhesion molecule Chemistry Myocardium Cardiovascular Agents Adhesion Amides Lymphocyte Function-Associated Antigen-1 Rats Cell Adhesion Process Solubility Cinnamates Biophysics Molecular Medicine |
| Zdroj: | Journal of Medicinal Chemistry. 44:2913-2920 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm010059w |
| Popis: | The interaction of LFA-1 and ICAM-1 plays an important role in the cell adhesion process. On the basis of previously reported SAR and structural information on the binding of our p-arylthiocinnamide series to LFA-1, we have identified the cyclic amide (C-ring) as a site for modification. Improvement in potency and, more importantly, in the physical properties and pharmacokinetic profiles of the leading compounds resulted from this modification. One of the best compounds (11f) is also shown to reduce myocardial infarct size in rat. |
| Databáze: | OpenAIRE |
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