Organic/AbbVie Seminar – Dr. Roberto Risi (AbbVie)

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1315 Seminar Hall
@ 2:00 pm - 3:00 pm

Dr. Rob Risi

Title: Discovery and Synthesis of Macrocyclic MCL-1 Inhibitor ABBV-467


ABBV-467 is a highly potent and selective MCL-1 inhibitor that was advanced to a phase I clinical trial for the treatment of multiple myeloma. Due to its large size and structural complexity, ABBV-467 is a challenging synthetic target. Herein, we describe the synthesis of ABBV-467 on a decagram scale, which enabled preclinical characterization. The strategy is convergent and stereoselective, featuring a hindered biaryl cross coupling, enantioselective hydrogenation, and conformationally preorganized macrocyclization by C–O bond formation as key steps.


After completing my PhD with Steve Burke at UW Madison, I started working in a research and development position at Abbvie. Specifically I work in the Centralized Organic Synthesis Group (COSG) within Discovery Research. Our group bridges the gap between Medicinal Chemistry and Process Chemistry. We focus on chemistry development and route optimization to enable synthesis of complex advance intermediates and API on decagram to hundreds of gram scale. We support discovery project teams by enabling the delivery of high quality API for advanced pre-clinical studies that often require decagram quantities. Most of the time our synthetic routes are basis for GLP campaigns as well.

Keywords: Synthesis, Macrocyclization, Apoptosis, MCL1

Host: Prof. Jennifer Schomaker