biostudies-literatureJordan AMCancer Research UK2724-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC4896930biostudies-literatureUnknown26(11)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.Bioorganic & medicinal chemistry lettersAnilinoquinazoline inhibitors of the RET kinase domain-Elaboration of the 7-position.PMC48969302046517098C480/A11411Hopkins GVMarch HNHamilton NMSmall HFWaddell IDWaszkowycz BOgilvie DJBegum HWatson AJJordan AMFairweather ELyons AJGoldberg KVishwanath SFritzl SNewton RfalseAnilinoquinazoline 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 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.2016-01-01T00:00:00Z2016 Jun2026-05-29T23:56:34.516Z2019-03-27T02:15:31ZS-EPMC48969302708612110.1016/j.bmcl.2016.03.100