title: Synthesis and evaluation of novel pyrimidine-based dual EGFR/Her-2 inhibitors.
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).
authors.affiliation: Shionogi Medicinal Research Laboratories, Shionogi & Co., Ltd, Fukushima-ku, Osaka, Japan. naoyuki.suzuki@shionogi.co.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Suzuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shiota
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Watanabe
authors.forename: Norihiro
authors.initials: N
authors.lastname: Haga
authors.forename: Takami
authors.initials: T
authors.lastname: Murashi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ohara
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuo
authors.forename: Naoki
authors.initials: N
authors.lastname: Oomori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yari
authors.forename: Keiji
authors.initials: K
authors.lastname: Dohi
authors.forename: Makiko
authors.initials: M
authors.lastname: Inoue
authors.forename: Motofumi
authors.initials: M
authors.lastname: Iguchi
authors.forename: Jyunko
authors.initials: J
authors.lastname: Sentou
authors.forename: Tooru
authors.initials: T
authors.lastname: Wada
mesh_terms: D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D066246:ErbB Receptors; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C030986:pyrimidine