Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability

Qingsong Liu; Jinhua Wang; Seong A. Kang; Carson C. Thoreen; Wooyoung Hur; Hwan Geun Choi; David L. Waller; Taebo Sim; David M. Sabatini; Nathanael S. Gray

doi:10.1016/j.bmcl.2011.04.129

Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability

Qingsong Liu, Jinhua Wang, Seong A. Kang, Carson C. Thoreen, Wooyoung Hur, Hwan Geun Choi, David L. Waller, Taebo Sim, David M. Sabatini, Nathanael S. Gray

KU-KIST Graduate School of Converging Science and Technology

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Starting from small molecule mTOR inhibitor Torin1, replacement of the piperazine ring with a phenyl ring resulted in a new series of mTOR inhibitors (as exemplified by 10) that showed superior potency and selectivity for mTOR, along with significantly improved mouse liver microsome stability and a longer in vivo half-life.

Original language	English
Pages (from-to)	4036-4040
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	13
DOIs	https://doi.org/10.1016/j.bmcl.2011.04.129
Publication status	Published - 2011 Jul 1

Keywords

PI3K
Torin1
mTOR

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2011.04.129

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Liu, Q., Wang, J., Kang, S. A., Thoreen, C. C., Hur, W., Choi, H. G., Waller, D. L., Sim, T., Sabatini, D. M., & Gray, N. S. (2011). Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability. Bioorganic and Medicinal Chemistry Letters, 21(13), 4036-4040. https://doi.org/10.1016/j.bmcl.2011.04.129

Liu, Q, Wang, J, Kang, SA, Thoreen, CC, Hur, W, Choi, HG, Waller, DL, Sim, T, Sabatini, DM & Gray, NS 2011, 'Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 13, pp. 4036-4040. https://doi.org/10.1016/j.bmcl.2011.04.129

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AU - Liu, Qingsong

AU - Wang, Jinhua

AU - Kang, Seong A.

AU - Thoreen, Carson C.

AU - Hur, Wooyoung

AU - Choi, Hwan Geun

AU - Waller, David L.

AU - Sim, Taebo

AU - Sabatini, David M.

AU - Gray, Nathanael S.

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Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability

Abstract

Keywords

ASJC Scopus subject areas

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