- Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: The discovery of AZD8055 and AZD2014
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The optimization of a potent and highly selective series of dual mTORC1 and mTORC2 inhibitors is described. An initial focus on improving cellular potency whilst maintaining or improving other key parameters, such as aqueous solubility and margins over hERG IC50, led to the discovery of the clinical candidate AZD8055 (14). Further optimization, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014 (21).
- Pike, Kurt G.,Malagu, Karine,Hummersone, Marc G.,Menear, Keith A.,Duggan, Heather M.E.,Gomez, Sylvie,Martin, Niall M.B.,Ruston, Linette,Pass, Sarah L.,Pass, Martin
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p. 1212 - 1216
(2013/03/14)
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- COMPOSITION AND PROCESS - 356
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There is provided a process for the preparation of a compound of Formula 1, the use of said process in the preparation of a compound of Formula 5 or a phosphate, sulphate, hydrogensulphate, malate, citrate, tartrate or fumarate salt thereof, and the use of the fumarate salt in a composition for use in therapy.
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Page/Page column 31-32
(2009/12/28)
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- 2-METHYLMORPHOLINE PYRIDO-, PYRAZO- AND PYRIMIDO-PYRIMIDINE DERIVATIVES AS MTOR INHIBITORS
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There is provided a compound of Formula (I), or a pharmaceutically acceptable salt thereof. There are also provided processes for the manufacture of a compound of Formula (1), and the use of a compound of Formula (1) as a medicament and in the treatment of cancer
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Page/Page column 122; 128
(2008/06/13)
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