| Title: | Dihydrothieno-pyridin-one and Tetrahydrothieno-azepin-one Inhibitors of Enhancer of Zeste Homologue 2 | ||
| Patent/Patent Application Number: | WO 2017/002064 Al | Publication date: | January 5, 2017 |
| Priority Application: | US 2015–62186550 | Priority date: | June 30, 2015 |
| Inventors: | Brackley, J. A., III; Graves, A. P., III; Knight, S. D.; Mcnulty, K. C.; Newlander, K. A.; Tian, X. | ||
| Assignee Company: | GlaxoSmithKline Intellectual Property (No.2) Limited, UK | ||
| Disease Area: | Cancer | Biological Target: | Enhancer of Zeste Homologue 2 (EZF2) |
| Summary: | The present application claims a series of dihydrothieno-pyridin-one and tetrahydrothieno-azepin-one derivatives as inhibitors of Enhancer of Zeste Homologue 2 (EZF2). EZF2 is the catalytic subunit of PRC2, which functions to silence target genes by trimethylating lysine 27 of histone H3. Histone H3 is an important protein in the field of epigenetics. The compounds described here are potentially useful in the treatment of prostate, breast, skin, bladder, kidney, liver, pancreas, ovarian, head, and neck cancer. |
| Important Compound Classes: |  |
| Key Structures: |  |
| Biological Assay: | The activity of the compounds to inhibit the methyltransferase activity of EZH2 within the PRC2 complex was measured in scintillation proximity assay. |
| Pharmacological Data: |
In vitro and in vivo testing
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| Synthesis: | The synthesis and biochemical activity of 14 compounds are described. |
The author declares no competing financial interest.