2. Academic Validation
  3. Design and synthesis of tetrahydropyridothieno[2,3-d]pyrimidine scaffold based epidermal growth factor receptor (EGFR) kinase inhibitors: the role of side chain chirality and Michael acceptor group for maximal potency

Design and synthesis of tetrahydropyridothieno[2,3-d]pyrimidine scaffold based epidermal growth factor receptor (EGFR) kinase inhibitors: the role of side chain chirality and Michael acceptor group for maximal potency

  • J Med Chem. 2010 Oct 28;53(20):7316-26. doi: 10.1021/jm100607r.
Chia-Hsien Wu 1,  Mohane Selvaraj Coumar,  Chang-Ying Chu,  Wen-Hsing Lin,  Yi-Rong Chen,  Chiung-Tong Chen,  Hui-Yi Shiao,  Shaik Rafi,  Sing-Yi Wang,  Hui Hsu,  Chun-Hwa Chen,  Chun-Yu Chang,  Teng-Yuan Chang,  Tzu-Wen Lien,  Ming-Yu Fang,  Kai-Chia Yeh,  Ching-Ping Chen,  Teng-Kuang Yeh,  Su-Huei Hsieh,  John T-A Hsu,  Chun-Chen Liao,  Yu-Sheng Chao,  Hsing-Pang Hsieh
Affiliations

Affiliation

  • 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, ROC.
PMID: 20961149 DOI: 10.1021/jm100607r
Abstract

HTS hit 7 was modified through hybrid design strategy to introduce a chiral side chain followed by introduction of Michael acceptor group to obtain potent EGFR kinase inhibitors 11 and 19. Both 11 and 19 showed over 3 orders of magnitude enhanced HCC827 antiproliferative activity compared to HTS hit 7 and also inhibited gefitinib-resistant double mutant (DM, T790M/L858R) EGFR kinase at nanomolar concentration. Moreover, treatment with 19 shrinked tumor in nude mice xenograft model.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-171252
    EGFR Inhibitor