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: Tetsuo Asaki, Yukiteru Sugiyama, Taisuke Hamamoto, Masaya Higashioka, Masato Umehara, Haruna Naito, Tomoko Niwa
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 16 Issue 5 Pg. 1421-5 (Mar 01 2006) ISSN: 0960-894X [Print] England
• PMID: 16332440 (Publication Type: Journal Article)

Chemical References

• Benzamides
• Protein Kinase Inhibitors
• benzamide
• Fusion Proteins, bcr-abl

Topics

• Benzamides (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Design
• Fusion Proteins, bcr-abl (antagonists & inhibitors, chemistry, metabolism)
• Humans
• Models, Molecular
• Molecular Structure
• Protein Kinase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Protein Structure, Tertiary
• Structure-Activity Relationship