title: Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity.
abstract: Pyrimidinyl pyrazole derivatives 1-4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound 2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound 2 and colchicine.
authors.affiliation: Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co. Ltd., 16-13, Kita-kasai 1-chome, Edogawa-ku, 134, Tokyo, Japan. okihi10g@daiichipharm.co.jp
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohki
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirotani
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Naito
authors.forename: Satoru
authors.initials: S
authors.lastname: Ohsuki
authors.forename: Megumi
authors.initials: M
authors.lastname: Minami
authors.forename: Akio
authors.initials: A
authors.lastname: Ejima
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Koiso
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008870:Microtubules / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects; D050257:Tubulin Modulators; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D011720:Pyrazoles; D011743:Pyrimidines; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine