Anilinoquinazoline inhibitors of the RET kinase domain-elaboration of the 7-position.
Authors
Jordan, Allan MBegum, Habiba
Fairweather, Emma E
Fritzl, Samantha J R
Goldberg, Kristin M
Hopkins, Gemma V
Hamilton, Niall M
Lyons, Amanda J
March, H Nikki
Newton, Rebecca
Small, Helen F
Vishwanath, S
Waddell, Ian D
Waszkowycz, Bohdan
Watson, Amanda J
Ogilvie, Donald J
Affiliation
Drug Discovery Unit, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, ManchesterIssue Date
2016-06-01
Metadata
Show full item recordAbstract
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.Citation
Anilinoquinazoline inhibitors of the RET kinase domain-elaboration of the 7-position. 2016, 26 (11):2724-9 Bioorg Med Chem LettJournal
Bioorganic & Medicinal Chemistry LettersDOI
10.1016/j.bmcl.2016.03.100PubMed ID
27086121Type
ArticleLanguage
enISSN
1464-3405ae974a485f413a2113503eed53cd6c53
10.1016/j.bmcl.2016.03.100