title: Design and synthesis of 3-substituted benzamide derivatives as Bcr-Abl kinase inhibitors.
abstract: A series of 3-substituted benzamide derivatives structurally related to STI-571 (imatinib mesylate), a Bcr-Abl tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML), was prepared and evaluated for antiproliferative activity against the Bcr-Abl-positive leukemia cell line K562. About ten 3-halogenated and 3-trifluoromethylated benzamide derivatives were identified as highly potent Bcr-Abl kinase inhibitors. One of these, NS-187 (9b), is a promising new candidate Bcr-Abl inhibitor for the therapy of STI-571-resistant chronic myeloid leukemia.
authors.affiliation: Discovery Research Laboratories, Nippon Shinyaku Co, Ltd, 14 Nishinosho-Monguchi-Cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. t.asaki@po.nippon-shinyaku.co.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Asaki
authors.forename: Yukiteru
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Taisuke
authors.initials: T
authors.lastname: Hamamoto
authors.forename: Masaya
authors.initials: M
authors.lastname: Higashioka
authors.forename: Masato
authors.initials: M
authors.lastname: Umehara
authors.forename: Haruna
authors.initials: H
authors.lastname: Naito
authors.forename: Tomoko
authors.initials: T
authors.lastname: Niwa
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D047428:Protein Kinase Inhibitors; C037689:benzamide; D016044:Fusion Proteins, bcr-abl