2. Academic Validation
  3. Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014

Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014

  • Bioorg Med Chem Lett. 2013 Mar 1;23(5):1212-6. doi: 10.1016/j.bmcl.2013.01.019.
Kurt G Pike 1,  Karine Malagu,  Marc G Hummersone,  Keith A Menear,  Heather M E Duggan,  Sylvie Gomez,  Niall M B Martin,  Linette Ruston,  Sarah L Pass,  Martin Pass
Affiliations

Affiliation

  • 1 AstraZeneca, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. kurt.pike@astrazeneca.com
PMID: 23375793 DOI: 10.1016/j.bmcl.2013.01.019
Abstract

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 IC(50), 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).

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