1402002-80-5Relevant academic research and scientific papers
Trifluoromethyl Oxetanes: Synthesis and Evaluation as a tert-Butyl Isostere
Mukherjee, Paramita,Pettersson, Martin,Dutra, Jason K.,Xie, Longfei,am Ende, Christopher W.
, p. 1574 - 1577 (2017)
The synthesis of a new trifluoromethyl oxetane was developed using a Corey–Chaykovsky epoxidation/ring-expansion reaction of trifluoromethyl ketones. The reaction was shown to proceed under mild conditions and displays a broad substrate scope. The trifluoromethyl oxetane was also evaluated as a tert-butyl isostere in the context of the γ-secretase modulator (GSM) program. We demonstrate that the trifluoromethyl oxetane-containing GSM has decreased lipophilicity, improved lipophilic efficiency (LipE) and metabolic stability relative to the corresponding tert-butyl GSM analogue, thus highlighting several benefits of trifluoromethyl oxetane as a more polar tert-butyl isostere.
