5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.

5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Research Abstract Details 

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5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Abstract Text:

Harold Mastalerz,Ming Chang,Ping Chen,Brian E Fink,Ashvinikumar Gavai,Wen-Ching Han,Walter Johnson,David Langley,Francis Y Lee,Kenneth Leavitt,Punit Marathe,Derek Norris,Simone Oppenheimer,Bogdan Sleczka,James Tarrant,John S Tokarski,Gregory D Vite,Dolatrai M Vyas,Henry Wong,Tai W Wong,Hongjian Zhang,Guifen Zhang,

Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, 1c, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor.

5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Publishing Authors By Initials

H Mastalerz,M Chang,P Chen,BE Fink,A Gavai,WC Han,W Johnson,D Langley,FY Lee,K Leavitt,P Marathe,D Norris,S Oppenheimer,B Sleczka,J Tarrant,JS Tokarski,GD Vite,DM Vyas,H Wong,TW Wong,H Zhang,G Zhang,

For similar heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research abstracts see: heterocyclic compounds: heterocyclic compounds, 1-ring: triazines research

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5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Bioorganic & medicinal chemistry letters

VOLUME: 17

Page Numbers: 4947-54

Journal Abbreviation: Bioorg. Med. Chem. Lett.

ISSN: 0960-894X

DAY: 10

MONTH: 06

YEAR: 2007

5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Information

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LANGUAGE: eng

NlmUniqueID: 9107377

5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Keywords Mesh Terms:

KEYWORDS: Triazines

MESH TERMS: pharmacology

Chemical & Substance for Abstract: 5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases. Information

Substance Name: Receptor, erbB-2

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for 5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.

AFFILIATION: Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-1951, USA. harold.mastalerz@bms.com

Country: England

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MEDLINETA: Bioorg Med Chem Lett

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