| Title: | Imidazopyrazine Derivatives As Inhibitors of mTOR | ||
| Patent/Patent Application Number: | WO 2013/016160 A1 | Publication date: | January 31, 2013 |
| Priority Application: | US 2011-449017P | Priority date: | July 26, 2011 |
| Inventors: | Meng, Z.; Siddiqui, M. A.; Reddy, P. A. P. | ||
| Assignee Company: | Merck Sharp & Dohme Corp., USA | ||
| Disease Area: | Cancer | Biological Target: | Mammalian Target of Rapamycin (mTOR) Kinase |
| Summary: | This application claims a series of imidazopyrazine analogues that may provide a treatment for cancer. | ||
| Important Compound Classes: |  |
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| Definitions: | U is N or CH | ||
| Key Structures: |  |
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| Recent Review Articles: | Malaguti P.; Vari S.; Cognetti F.; Fabi A.. The mammalian target of rapamycin inhibitors in breast cancer: current evidence and future directions. Anticancer Res. 2013, 33 (1), 21–28. | ||
| Johnson S. C.; Rabinovitch P. S.; Kaeberlein M.. mTOR is a key modulator of aging and age-related disease. Nature 2013, 493 (7432), 338–345. | |||
| Biological Assay: | Compound inhibitory activity was evaluated using an HTRF mTOR enzyme assay. Inhibition of mTORC1 and mTORC2 was measured using an immunofluorescent cell-based assay. Inhibition of mTORC1 activity was measured by the reduction of the level of phosphorylated 4E-BP1Thr37/46 (p4E-BP1Thr37/46). Inhibition of mTORC2 activity was measured by the reduction of the level of phosphorylated AKTSer473 (pAKTSer473). | ||
| Pharmacological Data: |  |
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| Synthesis: | Preparation of 7 compounds. | ||
The authors declare no competing financial interest.