Brian Cox et al final.pdf (606.78 kB)
Escaping from flatland: substituted bridged pyrrolidine fragments with inherent three-dimensional character
journal contribution
posted on 2023-06-07, 06:52 authored by Brian Cox, Victor Zdorichenko, Philip B Cox, Kevin I Booker-Milburn, Romain Paumier, Luke D Elliott, Michael Robertson-Ralph, Graham BloomfieldThe 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.
History
Publication status
- Published
File Version
- Accepted version
Journal
ACS Medicinal Chemistry LettersISSN
1948-5875Publisher
American Chemical SocietyExternal DOI
Issue
6Volume
11Page range
1185-1190Department affiliated with
- Chemistry Publications
Notes
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.0c00039Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-04-27First Open Access (FOA) Date
2021-03-28First Compliant Deposit (FCD) Date
2020-04-27Usage metrics
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