2. Academic Validation
  3. Discovery of novel 5-alkynyl-4-anilinopyrimidines as potent, orally active dual inhibitors of EGFR and Her-2 tyrosine kinases

Discovery of novel 5-alkynyl-4-anilinopyrimidines as potent, orally active dual inhibitors of EGFR and Her-2 tyrosine kinases

  • Bioorg Med Chem Lett. 2012 Jan 1;22(1):456-60. doi: 10.1016/j.bmcl.2011.10.103.
Naoyuki Suzuki 1,  Takeshi Shiota,  Fumihiko Watanabe,  Norihiro Haga,  Takami Murashi,  Takafumi Ohara,  Kenji Matsuo,  Naoki Omori,  Hiroshi Yari,  Keiji Dohi,  Makiko Inoue,  Motofumi Iguchi,  Jyunko Sentou,  Tooru Wada
Affiliations

Affiliation

  • 1 Shionogi Medicinal Research Laboratories, Shionogi & Co., Ltd, 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan. naoyuki.suzuki@shionogi.co.jp
PMID: 22101132 DOI: 10.1016/j.bmcl.2011.10.103
Abstract

5-Alkenyl or 5-alkynyl-4-anilinopyrimidines were prepared and evaluated for in vitro inhibition of EGFR/Her-2 kinase activity and the growth of tumor cell lines (BT474 and N87). Several of these compounds inhibited the growth of BT474 and N87 at concentrations below 200nM. Structure-activity relationship studies revealed a critical role for the 5-alkynyl moieties. The representative compound 19 exhibited significant antitumor potency in a mouse xenograft model.

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