Synthesis and structure?activity?relationship of 3,4?Diaryl?1H?pyrrolo[2,3?b]pyridines as irreversible Inhibitors of mutant EGFR?L858R/T790M

Article abstract of DOI:10.1016/j.ejps.2018.11.021

The epidermal growth factor receptor (EGFR) is a well?validated drug target for the treatment of non?small cell lung cancer. Here we present an optimization approach and preliminary structure?activity relationship for 1H?pyrrolo[2,3?b]pyridines as covalent irreversible mutant EGFR inhibitors. We synthesized a focused library to investigate the effect of different aromatic substituents in the 4?position of this scaffold, interacting with the gatekeeper. We determined the activity of the synthesized compounds mutant EGFR enzyme assays and determined the selectivity over the wild type.

Full text of DOI:10.1016/j.ejps.2018.11.021

Accepted Manuscript
Synthesis
and
structure'activity'relationship
of
3
,4'Diaryl'1H'pyrrolo[2,3'b]pyridines as irreversible Inhibitors of
mutant EGFR'L858R/T790M
Marcel Günther, Julian Laux, Stefan Laufer
PII:
S0928-0987(18)30512-8
DOI:
https://doi.org/10.1016/j.ejps.2018.11.021
PHASCI 4755
Reference:
To appear in:
European Journal of Pharmaceutical Sciences
Received date:
Revised date:
Accepted date:
23 August 2018
26 October 2018
19 November 2018
Please cite this article as: Marcel Günther, Julian Laux, Stefan Laufer , Synthesis and
structure'activity'relationship of 3,4'Diaryl'1H'pyrrolo[2,3'b]pyridines as irreversible
Inhibitors of mutant EGFR'L858R/T790M. Phasci (2018), https://doi.org/10.1016/
j.ejps.2018.11.021
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