Synthesis, characterization and evaluation of pro-drugs of VLA-4 antagonists
A pro-drug strategy to identify orally efficacious VLA-4 antagonists is described. Potential pro-drugs were evaluated for their physical chemical characteristics and in vitro properties, including solubility, stability, permeability and plasma stability. Based on this characterization, promising com...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2004-04, Vol.14 (7), p.1651-1654 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Huryn, Donna M Ashwell, Susan Baudy, Reinhardt Dressen, Darren B Gallaway, William Grant, Francine S Konradi, Andrei Ley, Robert W Petusky, Susan Pleiss, Michael A Sarantakis, Dimitri Semko, Christopher M Sherman, Mary M Tio, Cesar Zhang, Lu |
| description | A pro-drug strategy to identify orally efficacious VLA-4 antagonists is described. Potential pro-drugs were evaluated for their physical chemical characteristics and in vitro properties, including solubility, stability, permeability and plasma stability. Based on this characterization, promising compounds were identified for in vivo pharmacokinetic evaluation. These studies resulted in the identification of a pro-drug that exhibited desirable blood levels in PK studies in several different species.
A pro-drug strategy to identify orally efficacious VLA-4 antagonists is described. |
| doi_str_mv | 10.1016/j.bmcl.2004.01.062 |
| format | Article |
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A pro-drug strategy to identify orally efficacious VLA-4 antagonists is described.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Adhesion</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Integrin alpha4beta1 - antagonists & inhibitors</subject><subject>Integrin alpha4beta1 - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Pharmacology. 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A pro-drug strategy to identify orally efficacious VLA-4 antagonists is described.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>15026043</pmid><doi>10.1016/j.bmcl.2004.01.062</doi><tpages>4</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Cell Adhesion Drug Evaluation, Preclinical - methods Integrin alpha4beta1 - antagonists & inhibitors Integrin alpha4beta1 - metabolism Male Medical sciences Miscellaneous Pharmacology. Drug treatments Physico-chemical characterization Pro-drugs Prodrugs - chemical synthesis Prodrugs - metabolism Rats VLA-4 antagonist |
| title | Synthesis, characterization and evaluation of pro-drugs of VLA-4 antagonists |
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