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Title: Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors

Abstract

Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model.

Authors:
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  1. BMS
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE
OSTI Identifier:
1002642
Resource Type:
Journal Article
Journal Name:
Bioorg. Med. Chem. Lett.
Additional Journal Information:
Journal Volume: 20; Journal Issue: (9) ; 05, 2010; Journal ID: ISSN 0960-894X
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; CARCINOMAS; CRYSTALLOGRAPHY; DESIGN; IN VIVO; LEAD COMPOUNDS; NEOPLASMS; PHOSPHOTRANSFERASES; STRUCTURE-ACTIVITY RELATIONSHIPS; SYNTHESIS

Citation Formats

Williams, David K, Chen, Xiao-Tao, Tarby, Christine, Kaltenbach, Robert, Cai, Zhen-Wei, Tokarski, John S, An, Yongmi, Sack, John S, Wautlet, Barri, Gullo-Brown, Johnni, Henley, Benjamin J, Jeyaseelan, Robert, Kellar, Kristen, Manne, Veeraswamy, Trainor, George L, Lombardo, Louis J, Fargnoli, Joseph, and Borzilleri, Robert M. Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors. United States: N. p., 2010. Web. doi:10.1016/j.bmcl.2010.01.042.
Williams, David K, Chen, Xiao-Tao, Tarby, Christine, Kaltenbach, Robert, Cai, Zhen-Wei, Tokarski, John S, An, Yongmi, Sack, John S, Wautlet, Barri, Gullo-Brown, Johnni, Henley, Benjamin J, Jeyaseelan, Robert, Kellar, Kristen, Manne, Veeraswamy, Trainor, George L, Lombardo, Louis J, Fargnoli, Joseph, & Borzilleri, Robert M. Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors. United States. https://doi.org/10.1016/j.bmcl.2010.01.042
Williams, David K, Chen, Xiao-Tao, Tarby, Christine, Kaltenbach, Robert, Cai, Zhen-Wei, Tokarski, John S, An, Yongmi, Sack, John S, Wautlet, Barri, Gullo-Brown, Johnni, Henley, Benjamin J, Jeyaseelan, Robert, Kellar, Kristen, Manne, Veeraswamy, Trainor, George L, Lombardo, Louis J, Fargnoli, Joseph, and Borzilleri, Robert M. 2010. "Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors". United States. https://doi.org/10.1016/j.bmcl.2010.01.042.
@article{osti_1002642,
title = {Design, synthesis and structure-activity relationships of novel biarylamine-based Met kinase inhibitors},
author = {Williams, David K and Chen, Xiao-Tao and Tarby, Christine and Kaltenbach, Robert and Cai, Zhen-Wei and Tokarski, John S and An, Yongmi and Sack, John S and Wautlet, Barri and Gullo-Brown, Johnni and Henley, Benjamin J and Jeyaseelan, Robert and Kellar, Kristen and Manne, Veeraswamy and Trainor, George L and Lombardo, Louis J and Fargnoli, Joseph and Borzilleri, Robert M},
abstractNote = {Biarylamine-based inhibitors of Met kinase have been identified. Lead compounds demonstrate nanomolar potency in Met kinase biochemical assays and significant activity in the Met-driven GTL-16 human gastric carcinoma cell line. X-ray crystallography revealed that these compounds adopt a bioactive conformation, in the kinase domain, consistent with that previously seen with 2-pyridone-based Met kinase inhibitors. Compound 9b demonstrated potent in vivo antitumor activity in the GTL-16 human tumor xenograft model.},
doi = {10.1016/j.bmcl.2010.01.042},
url = {https://www.osti.gov/biblio/1002642}, journal = {Bioorg. Med. Chem. Lett.},
issn = {0960-894X},
number = (9) ; 05, 2010,
volume = 20,
place = {United States},
year = {Fri Sep 03 00:00:00 EDT 2010},
month = {Fri Sep 03 00:00:00 EDT 2010}
}