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

Research output: Contribution to journalArticle

9 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 languageEnglish
Pages (from-to)4036-4040
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number13
DOIs
Publication statusPublished - 2011 Jul 1
Externally publishedYes

Fingerprint

Liver Microsomes
Microsomes
Liver
Half-Life
Molecules
piperazine

Keywords

  • mTOR
  • PI3K
  • Torin1

ASJC Scopus subject areas

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

Cite this

Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability. / Liu, Qingsong; Wang, Jinhua; Kang, Seong A.; Thoreen, Carson C.; Hur, Wooyoung; Choi, Hwan Geun; Waller, David L.; Sim, Taebo; Sabatini, David M.; Gray, Nathanael S.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 13, 01.07.2011, p. 4036-4040.

Research output: Contribution to journalArticle

Liu, Qingsong ; Wang, Jinhua ; Kang, Seong A. ; Thoreen, Carson C. ; Hur, Wooyoung ; Choi, Hwan Geun ; Waller, David L. ; Sim, Taebo ; Sabatini, David M. ; Gray, Nathanael S. / Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 13. pp. 4036-4040.
@article{ebd7922662e64fb4a4a46dd09c4d8b02,
title = "Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability",
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.",
keywords = "mTOR, PI3K, Torin1",
author = "Qingsong Liu and Jinhua Wang and Kang, {Seong A.} and Thoreen, {Carson C.} and Wooyoung Hur and Choi, {Hwan Geun} and Waller, {David L.} and Taebo Sim and Sabatini, {David M.} and Gray, {Nathanael S.}",
year = "2011",
month = "7",
day = "1",
doi = "10.1016/j.bmcl.2011.04.129",
language = "English",
volume = "21",
pages = "4036--4040",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "13",

}

TY - JOUR

T1 - Discovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability

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.

PY - 2011/7/1

Y1 - 2011/7/1

N2 - 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.

AB - 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.

KW - mTOR

KW - PI3K

KW - Torin1

UR - http://www.scopus.com/inward/record.url?scp=80955181164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80955181164&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2011.04.129

DO - 10.1016/j.bmcl.2011.04.129

M3 - Article

C2 - 21621413

AN - SCOPUS:80955181164

VL - 21

SP - 4036

EP - 4040

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 13

ER -