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Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position
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 physic...
| Autores principales: | , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Elsevier Science Ltd
2016
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896930/ https://www.ncbi.nlm.nih.gov/pubmed/27086121 http://dx.doi.org/10.1016/j.bmcl.2016.03.100 |
| _version_ | 1782436049203494912 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Jordan, Allan M. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-4896930 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2016 |
| publisher | Elsevier Science Ltd |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-48969302016-06-15 Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position 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. Bioorg Med Chem Lett Article 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. Elsevier Science Ltd 2016-06-01 /pmc/articles/PMC4896930/ /pubmed/27086121 http://dx.doi.org/10.1016/j.bmcl.2016.03.100 Text en © 2016 The Authors. Published by Elsevier Ltd. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| spellingShingle | Article 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. Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position |
| title | Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position |
| title_full | Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position |
| title_fullStr | Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position |
| title_full_unstemmed | Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position |
| title_short | Anilinoquinazoline inhibitors of the RET kinase domain—Elaboration of the 7-position |
| title_sort | anilinoquinazoline inhibitors of the ret kinase domain—elaboration of the 7-position |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896930/ https://www.ncbi.nlm.nih.gov/pubmed/27086121 http://dx.doi.org/10.1016/j.bmcl.2016.03.100 |
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