Synthesis and evaluation of novel pyrimidine-based dual EGFR/Her-2 inhibitors

  • Bioorg Med Chem Lett. 2011 Mar 15;21(6):1601-6. doi: 10.1016/j.bmcl.2011.01.119.
Naoyuki Suzuki  1 ,  Takeshi Shiota ,  Fumihiko Watanabe ,  Norihiro Haga ,  Takami Murashi ,  Takafumi Ohara ,  Kenji Matsuo ,  Naoki Oomori ,  Hiroshi Yari ,  Keiji Dohi ,  Makiko Inoue ,  Motofumi Iguchi ,  Jyunko Sentou ,  Tooru Wada
Affiliations
  • 1. Shionogi Medicinal Research Laboratories, Shionogi & Co., Ltd, Fukushima-ku, Osaka, Japan. [email protected]
PMID: 21334203 DOI: 10.1016/j.bmcl.2011.01.119
Abstract

A structure-activity relationship study of 4-anilinopyrimidines for dual EGFR/Her-2 inhibitor has resulted in the identification of 4-anilino-5-alkenyl or 5-alkynyl-6-methylpyrimidine derivatives that have exhibited effective inhibitory activity against both Enzymes. The presence of 5-alkenyl or 5-alkynyl moiety bearing terminal hydrophilic group played important role for inhibition of these Enzymes. Selected compounds in the series demonstrated some activity against Her-2 dependent cell line (BT474).