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Updated: May 8, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Synthesis and stability of oxetane analogs of thalidomide and lenalidomide
Johannes A Burkhard1, Georg Wuitschik, Jean-Marc Plancher
1Laboratorium für Organische Chemie, ETH Zürich, CH-8093 Zürich, Switzerland.
Abstract:
Oxetanes are used in drug discovery to enable physicochemical and metabolic property enhancement for the structures to which they are grafted. An imide C═O to oxetane swap on thalidomide and lenalidomide templates provides analogs with similar physicochemical and in vitro properties of the parent drugs, with an important exception: oxetane analog 2 displays a clear differentiation with respect to human plasma stability. The prospect of limiting in vivo stability/metabolism, blocking in vivo racemization, and potentially altering teratogenicity is appealing.
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