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Your search keyword '"Robert C. Armstrong"' showing total 2 results
Start Over Author "Robert C. Armstrong" Journal bioorganicmedicinal chemistry letters
2 results on '"Robert C. Armstrong"'

1. Discovery and optimization of a highly efficacious class of 5-aryl-2-aminopyridines as FMS-like tyrosine kinase 3 (FLT3) inhibitors

Author

Barbara Belli, Alan Dao, Robert C. Armstrong, Michael F. Gardner, Darren E. Insko, Sunny Abraham, Ron R. Nepomuceno, Gang Liu, Mark W. Holladay, Dana Gitnick, Daniel Brigham, Patrick P. Zarrinkar, Shimin Xu, Xing Liu, Allison M. Rooks, and Ron Christopher

Subjects
Clinical Biochemistry, Pharmaceutical Science, Aminopyridines, Antineoplastic Agents, Pharmacology, Biochemistry, chemistry.chemical_compound, In vivo, Drug Discovery, Humans, Molecular Biology, Tumor xenograft, Quizartinib, Cell Proliferation, CYP3A4, Dose-Response Relationship, Drug, Aryl, Organic Chemistry, Xenograft Model Antitumor Assays, chemistry, fms-Like Tyrosine Kinase 3, Tyrosine Kinase 3, Fms-Like Tyrosine Kinase 3, Molecular Medicine
Abstract

Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have designed de novo a simpler aminopyridine-based hinge binding motif. Further optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time-dependent inhibition resulted in a highly efficacious compound (6s) in tumor xenograft model for further preclinical development.

Published
2015

2. 4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors

Author

Michael Williams, Kelly G. Sprankle, Mark W. Holladay, Shripad Bhagwat, Qi Chao, Raffaella Faraoni, Dana Gitnick, Lan Tran, Joyce James, Sunny Abraham, Andiliy G. Lai, Brian T. Campbell, Martin W. Rowbottom, Ruwanthi N. Gunawardane, Bruce R. Ruggeri, Michael F. Gardner, Robert C. Armstrong, Mark A. Ator, Bruce D. Dorsey, Eduardo Setti, and Merryl D. Cramer

Subjects
Proto-Oncogene Proteins B-raf, Stereochemistry, Clinical Biochemistry, Mutant, Substituent, Pharmaceutical Science, Stereoisomerism, Biochemistry, chemistry.chemical_compound, Mice, Structure-Activity Relationship, Drug Discovery, Structure–activity relationship, Animals, Urea, Tissue Distribution, Molecular Biology, Protein Kinase Inhibitors, Dose-Response Relationship, Drug, Molecular Structure, Kinase, Chemistry, Aryl, Organic Chemistry, Wild type, Xenograft Model Antitumor Assays, Rats, Quinazolines, Molecular Medicine
Abstract

Aryl phenyl ureas with a 4-quinazolinoxy substituent at the meta-position of the phenyl ring are potent inhibitors of mutant and wild type BRAF kinase. Compound 7 (1-(5-tert-butylisoxazol-3-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy)phenyl)urea hydrochloride) exhibits good pharmacokinetic properties in rat and mouse and is efficacious in a mouse tumor xenograft model following oral dosing.

Published
2011

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