Imidazo[1,2-a]pyridin-6-yl-benzamide analogs as potent RAF inhibitors

• Published in: Bioorganic & medicinal chemistry letters 2017-12, Vol.27 (23), p.5221-5224
• Main Authors: Smith, Aaron, Ni, Zhi-Jie, Poon, Daniel, Huang, Zilin, Chen, Zheng, Zhang, Qiong, Tandeske, Laura, Merritt, Hanne, Shoemaker, Kevin, Chan, John, Kaufman, Susan, Huh, Kay, Murray, Jeremy, Appleton, Brent A., Cowan-Jacob, Sandra W., Scheufler, Clemens, Kanazawa, Takanori, Jansen, Johanna M., Stuart, Darrin, Shafer, Cynthia M.
• Format: Article
• Language: English
• Subjects: Benzamides - chemical synthesis; Benzamides - chemistry; Benzamides - pharmacology; Dose-Response Relationship, Drug; Heterocyclic Compounds, 2-Ring - chemical synthesis; Heterocyclic Compounds, 2-Ring - chemistry; Heterocyclic Compounds, 2-Ring - pharmacology; Humans; Kinase; MAPK; Models, Molecular; Molecular Structure; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Proto-Oncogene Proteins B-raf - antagonists & inhibitors; Proto-Oncogene Proteins B-raf - metabolism; RAF; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.10.047

A series of imidazo[1,2-a]pyridin-6-yl-benzamide analogs were designed as inhibitors of B-RAFV600E. Medicinal chemistry techniques were employed to explore the SAR for this series and improve selectivity versus P38 and VEGFR2. [Display omitted] A series of imidazo[1,2-a]pyridin-6-yl-benzamide analogs was designed as inhibitors of B-RAFV600E. Medicinal chemistry techniques were employed to explore the SAR for this series and improve selectivity versus P38 and VEGFR2.