| Autor: |
Cohen F; Department of Discovery Chemistry, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States. fcohen@gene.com, Bergeron P, Blackwood E, Bowman KK, Chen H, Dipasquale AG, Epler JA, Koehler MF, Lau K, Lewis C, Liu L, Ly CQ, Malek S, Nonomiya J, Ortwine DF, Pei Z, Robarge KD, Sideris S, Trinh L, Truong T, Wu J, Zhao X, Lyssikatos JP |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2011 May 12; Vol. 54 (9), pp. 3426-35. Date of Electronic Publication: 2011 Apr 15. |
| DOI: |
10.1021/jm200215y |
| Abstrakt: |
A series of inhibitors of mTOR kinase based on a quaternary-substituted dihydrofuropyrimidine was designed and synthesized. The most potent compounds in this series inhibited mTOR kinase with K(i) < 1.0 nM and were highly (>100×) selective for mTOR over the closely related PI3 kinases. Compounds in this series showed inhibition of the pathway and antiproliferative activity in cell-based assays. Furthermore, these compounds had excellent mouse PK, and showed a robust PK-PD relationship in a mouse model of cancer. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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