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Published on: June 10, 2021
Escaping from Flatland: Substituted Bridged Pyrrolidine Fragments with Inherent Three-Dimensional Character
Brian Cox1,2, Victor Zdorichenko2, Philip B Cox3
1School of Life Sciences, University of Sussex, Brighton BN1 9QJ, U.K.
Abstract:
The pressure to deliver new medicines to the patient continues to grow along with increases in compound failure rate, thus putting the current R&D model at risk. Analysis has shown that increasing the three-dimensionality of potential drug candidates decreases the risk of failure and improves binding selectivity and frequency. For this reason many workers have taken a new look at the power of photochemistry as a means to generate novel sp3 rich scaffolds for use in drug discovery programs. Here we report the design, synthesis, and computational structural analysis of a series of 2,4-methanoprolines having inherent 3D character (PMI and PBF scores) significantly higher than that of the broader AbbVie Rule of 3 (Ro3) collection.
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