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

Naoyuki Suzuki; 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

doi:10.1016/j.bmcl.2011.01.119

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. Epub 2011 Feb 2.

Authors

Naoyuki Suzuki¹, 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

Affiliation

¹ Shionogi Medicinal Research Laboratories, Shionogi & Co., Ltd, Fukushima-ku, Osaka, Japan. naoyuki.suzuki@shionogi.co.jp

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).

MeSH terms

Crystallography, X-Ray
Drug Evaluation, Preclinical
ErbB Receptors / antagonists & inhibitors*
ErbB Receptors / chemistry
Humans
Models, Molecular
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
Receptor, ErbB-2 / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Pyrimidines
ERBB2 protein, human
ErbB Receptors
Receptor, ErbB-2
pyrimidine