Literature DB >> 16777410

Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series.

Kimberly G Petrov1, Yue-Mei Zhang, Malcolm Carter, G Stuart Cockerill, Scott Dickerson, Cassandra A Gauthier, Yu Guo, Robert A Mook, David W Rusnak, Ann L Walker, Edgar R Wood, Karen E Lackey.   

Abstract

Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme activity, but appeared to dramatically affect the cellular efficacy. The discovery of lapatinib emerged from this work.

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Year:  2006        PMID： 16777410     DOI： 10.1016/j.bmcl.2006.05.090

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  20 in total

1.  Measuring and interpreting the selectivity of protein kinase inhibitors.

Authors:  Lynette A Smyth; Ian Collins
Journal:  J Chem Biol       Date:  2009-06-06

2.  Synergistic enhancement of the potency and selectivity of small molecule transcriptional inhibitors.

Authors:  Christopher E Taylor; Quintin Pan; Anna K Mapp
Journal:  ACS Med Chem Lett       Date:  2012-01-12       Impact factor: 4.345

3.  Design and synthesis of novel Gefitinib analogues with improved anti-tumor activity.

Authors:  Xiaoqing Wu; Mingdong Li; Yang Qu; Wenhua Tang; Youguang Zheng; Jiqin Lian; Min Ji; Liang Xu
Journal:  Bioorg Med Chem       Date:  2010-04-21       Impact factor: 3.641

4.  In vitro enzymatic characterization of near full length EGFR in activated and inhibited states.

Authors:  Chen Qiu; Mary K Tarrant; Tatiana Boronina; Patti A Longo; Jennifer M Kavran; Robert N Cole; Philip A Cole; Daniel J Leahy
Journal:  Biochemistry       Date:  2009-07-21       Impact factor: 3.162

5.  2-Chloro-1-(3-fluoro-benz-yloxy)-4-nitro-benzene.

Authors:  Hui-Ling Yu
Journal:  Acta Crystallogr Sect E Struct Rep Online       Date:  2009-09-05

6.  Kinase scaffold repurposing for neglected disease drug discovery: discovery of an efficacious, lapatinib-derived lead compound for trypanosomiasis.

Authors:  Gautam Patel; Caitlin E Karver; Ranjan Behera; Paul J Guyett; Catherine Sullenberger; Peter Edwards; Norma E Roncal; Kojo Mensa-Wilmot; Michael P Pollastri
Journal:  J Med Chem       Date:  2013-05-03       Impact factor: 7.446

7.  Mechanism of activation and inhibition of the HER4/ErbB4 kinase.

Authors:  Chen Qiu; Mary K Tarrant; Sung Hee Choi; Aruna Sathyamurthy; Ron Bose; Sudeep Banjade; Ashutosh Pal; William G Bornmann; Mark A Lemmon; Philip A Cole; Daniel J Leahy
Journal:  Structure       Date:  2008-03       Impact factor: 5.006

8.  Design, synthesis and biological evaluation of substituted pyrrolo[2,3-d]pyrimidines as multiple receptor tyrosine kinase inhibitors and antiangiogenic agents.

Authors:  Aleem Gangjee; Ojas A Namjoshi; Jianming Yu; Michael A Ihnat; Jessica E Thorpe; Linda A Warnke
Journal:  Bioorg Med Chem       Date:  2008-04-14       Impact factor: 3.641

9.  Activity of lapatinib is independent of EGFR expression level in HER2-overexpressing breast cancer cells.

Authors:  Dongwei Zhang; Ashutosh Pal; William G Bornmann; Fumiyuki Yamasaki; Francisco J Esteva; Gabriel N Hortobagyi; Chandra Bartholomeusz; Naoto T Ueno
Journal:  Mol Cancer Ther       Date:  2008-07       Impact factor: 6.261

10.  Assessment of epidermal growth factor receptor (EGFR, ErbB1) and HER2 (ErbB2) protein expression levels and response to lapatinib (Tykerb, GW572016) in an expanded panel of human normal and tumour cell lines.

Authors:  D W Rusnak; K J Alligood; R J Mullin; G M Spehar; C Arenas-Elliott; A-M Martin; Y Degenhardt; S K Rudolph; T F Haws; B L Hudson-Curtis; T M Gilmer
Journal:  Cell Prolif       Date:  2007-08       Impact factor: 6.831
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