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(A) The rate limiting step in the synthesis of NAD+ is the NAMPT catalyzed synthesis of NMN from NAM and PRPP. (B) Our initial identification of the azetidine ureas came from a scaffold morph of the previously established cyclopropyl carboxamide NAMPT inhibitors. (C) Synthesis of the five and six membered ring ureas demonstrates the superiority of the azetidine urea for NAMPT inhibition.
