Escaping from flatland: substituted bridged pyrrolidine fragments with inherent three-dimensional character

Cox, Brian, Zdorichenko, Victor, Cox, Philip B, Booker-Milburn, Kevin I, Paumier, Romain, Elliott, Luke D, Robertson-Ralph, Michael and Bloomfield, Graham (2020) Escaping from flatland: substituted bridged pyrrolidine fragments with inherent three-dimensional character. ACS Medicinal Chemistry Letters, 11 (6). pp. 1185-1190. ISSN 1948-5875

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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.

Item Type: Article
Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsmedchemlett.0c00039
Schools and Departments: School of Life Sciences > Chemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 27 Apr 2020 07:27
Last Modified: 28 Mar 2021 01:00
URI: http://sro.sussex.ac.uk/id/eprint/91031

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