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A Potent and Selective Janus Kinase Inhibitor with a Chiral 3D‐Shaped Triquinazine Ring System from Chemical Space

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Meier Kris, Arús‐Pous Josep, Reymond Jean‐Louis,
Project Chemical Space Design of Small Molecules and Peptides
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Original article (peer-reviewed)

Journal Angewandte Chemie International Edition
Volume (Issue) 60(4)
Page(s) 2074 - 2077
Title of proceedings Angewandte Chemie International Edition
DOI 10.1002/anie.v60.4


The generated databases (GDBs) enumerate billions of possible molecules following simple rules of chemical stability and synthetic feasibility. Exploring the GDBs shows that many chiral, 3D-shaped ring systems, often containing quaternary centers, have never been exploited for drug design. Shown herein is that such ring systems can be useful for medicinal chemistry by using the example of the enantioselective synthesis of triquinazine, a novel chiral piperazine analogue derived from angular triquinane. It is used to design a nanomolar and selective inhibitor of Janus Kinase 1 and is related to the marketed drug Tofacitinib, which is useful for treating autoimmune diseases.