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Tyrosine Kinase Inhibitors. 20. Optimization of Substituted Quinazoline and Pyrido[3,4-d]pyrimidine Derivatives as Orally Active, Irreversible Inhibitors of the Epidermal Growth Factor Receptor Family

Overview of attention for article published in Journal of Medicinal Chemistry, August 2016
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (76th percentile)
  • Good Attention Score compared to outputs of the same age and source (67th percentile)

Mentioned by

twitter
1 tweeter
patent
3 patents

Citations

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43 Dimensions

Readers on

mendeley
49 Mendeley
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Title
Tyrosine Kinase Inhibitors. 20. Optimization of Substituted Quinazoline and Pyrido[3,4-d]pyrimidine Derivatives as Orally Active, Irreversible Inhibitors of the Epidermal Growth Factor Receptor Family
Published in
Journal of Medicinal Chemistry, August 2016
DOI 10.1021/acs.jmedchem.6b00883
Pubmed ID
Authors

Jeff B. Smaill, Andrea J. Gonzales, Julie A. Spicer, Helen Lee, Jessica E. Reed, Karen Sexton, Irene W. Althaus, Tong Zhu, Shannon L. Black, Adrian Blaser, William A. Denny, Paul A. Ellis, Stephen Fakhoury, Patricia J. Harvey, Ken Hook, Florence O. J. McCarthy, Brian D. Palmer, Freddy Rivault, Kevin Schlosser, Teresa Ellis, Andrew M. Thompson, Erin Trachet, R. Thomas Winters, Haile Tecle, Alexander Bridges

Abstract

Structure-activity relationships for inhibition of erbB1, erbB2 and erbB4 were determined for a series of quinazoline- and pyrido[3,4-d]pyrimidine-based analogues of the irreversible pan-erbB inhibitor, canertinib. Cyclic amine bearing crotonamides were determined to provide rapid inhibition of cellular erbB1 autophosphorylation and good metabolic stability in liver microsome and hepatocyte assays. The influence of 4-anilino substitution on pan-erbB inhibitory potency was investigated. Several anilines were identified as providing potent, reversible pan-erbB inhibition. Optimum 4- and 6-substituents with known 7-substituents provided preferred irreversible inhibitors for pharmacodynamic testing in vivo. Quinazoline 54 and pyrido[3,4-d]pyrimidine 71 were identified as clearly superior to canertinib. Both compounds possess a piperidinyl crotonamide Michael acceptor and a 3-chloro-4-fluoroaniline, indicating these as optimized 6- and 4-substituents respectively. Pharmacokinetic comparison of compounds 54 and 71 across three species selected compound 54 as the preferred candidate. Compound 54 (PF-00299804) has been assigned the nomenclature of dacomitinib and is currently under clinical evaluation.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 1 2%
Germany 1 2%
Unknown 47 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 11 22%
Researcher 9 18%
Student > Master 4 8%
Student > Doctoral Student 3 6%
Other 3 6%
Other 7 14%
Unknown 12 24%
Readers by discipline Count As %
Chemistry 23 47%
Pharmacology, Toxicology and Pharmaceutical Science 5 10%
Biochemistry, Genetics and Molecular Biology 3 6%
Agricultural and Biological Sciences 2 4%
Business, Management and Accounting 1 2%
Other 4 8%
Unknown 11 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 March 2022.
All research outputs
#3,837,614
of 21,332,267 outputs
Outputs from Journal of Medicinal Chemistry
#5,916
of 21,551 outputs
Outputs of similar age
#62,260
of 287,099 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#47
of 174 outputs
Altmetric has tracked 21,332,267 research outputs across all sources so far. Compared to these this one has done well and is in the 81st percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 21,551 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has gotten more attention than average, scoring higher than 71% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 287,099 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 174 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.