Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position
| Autor: | Jordan, Allan M., Begum, Habiba, Fairweather, Emma, Fritzl, Samantha, Goldberg, Kristin, Hopkins, Gemma V., Hamilton, Niall M., Lyons, Amanda J., March, H. Nikki, Newton, Rebecca, Small, Helen F., Vishwanath, Swamy, Waddell, Ian D., Waszkowycz, Bohdan, Watson, Amanda J., Ogilvie, Donald J. |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular Kinase inhibitor Aniline Compounds Dose-Response Relationship Drug Molecular Structure Organic Chemistry Clinical Biochemistry Proto-Oncogene Proteins c-ret Pharmaceutical Science Biochemistry Article Targeted therapy Structure-Activity Relationship Hepatocyte stability Drug Discovery RET receptor Quinazolines Molecular Medicine Humans Lung cancer Molecular Biology Protein Kinase Inhibitors ComputingMethodologies_COMPUTERGRAPHICS |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters |
| ISSN: | 1464-3405 0960-894X |
| Popis: | Graphical abstract We have previously reported a series of anilinoquinazoline derivatives as potent and selective biochemical inhibitors of the RET kinase domain. However, these derivatives displayed diminished cellular potency. Herein we describe further optimisation of the series through modification of their physicochemical properties, delivering improvements in cell potency. However, whilst cellular selectivity against key targets could be maintained, combining cell potency and acceptable pharmacokinetics proved challenging. |
| Databáze: | OpenAIRE |
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