AZD4320 is a dual Bcl2/Bcl-x<sub>L</sub> inhibitor that has been nominated for clinical development. The compound is relatively large (MW 945), hydrophobic (clogP 9.6), and contains two chiral centers. Early syntheses relied on chiral resolutions of racemic material, and the overall routes were &gt;15 steps in length. As part of our medicinal chemistry route development process, we wanted to provide efficient syntheses to chiral intermediates and enable late-stage diversification of important functionalities. There was also a drive to prepare phosphate prodrugs to improve formulation, which offered an additional level of difficulty in terms of handling and stability. In this poster we describe the evolution of medicinal chemistry routes used to prepare AZD4320, its prodrugs, and related analogs.

Preclinical synthetic routes to the dual Bcl2/Bcl-x<sub>L</sub> inhibitor AZD4320 and related prodrugs and analogs

250th National Meeting (2015)

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Preclinical synthetic routes to the dual Bcl2/Bcl-xL inhibitor AZD4320 and related prodrugs and analogs

Preclinical synthetic routes to the dual Bcl2/Bcl-x_L inhibitor AZD4320 and related prodrugs and analogs