Premium
A Potent and Selective Janus Kinase Inhibitor with a Chiral 3D‐Shaped Triquinazine Ring System from Chemical Space
Author(s) -
Meier Kris,
ArúsPous Josep,
Reymond JeanLouis
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202012049
Subject(s) - tofacitinib , chemical space , ring (chemistry) , combinatorial chemistry , enantioselective synthesis , chemistry , piperazine , janus , janus kinase inhibitor , stereochemistry , molecule , drug discovery , janus kinase , nanotechnology , kinase , materials science , organic chemistry , biology , biochemistry , rheumatoid arthritis , immunology , catalysis
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.