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

Authors :: Liu Q
Wang J
Kang SA
Thoreen CC
Hur W
Choi HG
Waller DL
Sim T
Sabatini DM
Gray NS
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Jul 01; Vol. 21 (13), pp. 4036-40. Date of Electronic Publication: 2011 May 07.
Publication Year :: 2011
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.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Subjects :: Animals
Cells, Cultured
Drug Stability
Enzyme Activation drug effects
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Inhibitory Concentration 50
Mice
Molecular Structure
Naphthyridines chemistry
Naphthyridines pharmacology
Drug Discovery
Microsomes, Liver drug effects
Naphthyridines chemical synthesis
TOR Serine-Threonine Kinases antagonists & inhibitors

Full Text Access

Tools