Core refinement toward permeable β-secretase (BACE-1) inhibitors with low hERG activity

T Ginman, J Viklund, J Malmström, J Blid…

文献索引：Ginman, Tobias; Viklund, Jenny; Malmstroem, Jonas; Blid, Jan; Emond, Rikard; Forsblom, Rickard; Johansson, Anh; Kers, Annika; Lake, Fredrik; Sehgelmeble, Fernando; Sterky, Karin J.; Bergh, Margareta; Lindgren, Anders; Johansson, Patrik; Jeppsson, Fredrik; Faelting, Johanna; Gravenfors, Ylva; Rahm, Fredrik Journal of Medicinal Chemistry, 2013 , vol. 56, # 11 p. 4181 - 4205

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被引用次数: 25

摘要

By use of iterative design aided by predictive models for target affinity, brain permeability, and hERG activity, novel and diverse compounds based on cyclic amidine and guanidine cores were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease. Since synthesis feasibility had low priority in the design of the cores, an extensive synthesis effort was needed to make the relevant compounds. Syntheses of ...