Electron‐transfer reductions of unactivated aryl and alkyl iodides with a neutral ground‐state organic molecule are reported. The reducing agent 1 is formed in two steps from N‐methylbenzimidazole using very simple chemistry, and subsequent treatment of the iodoalkane or ‐arene with 1 affords cyclized products (see scheme).
We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.
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