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A Potent and Selective Janus Kinase Inhibitor with a Chiral 3D‐Shaped Triquinazine Ring System from Chemical Space
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 her...
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Published in: | Angewandte Chemie 2021-01, Vol.133 (4), p.2102-2105 |
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Main Authors: | , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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.
Exploring the chemical‐space database GDB4c for novel chiral ring systems led to the design and synthesis of triquinazine and a functionalized analogue showing nanomolar inhibition of Janus Kinases. |
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ISSN: | 0044-8249 1521-3757 |
DOI: | 10.1002/ange.202012049 |