逃离平面世界：具有固有三维特征的取代桥连吡咯烷片段
Escaping from Flatland: Substituted Bridged Pyrrolidine Fragments with Inherent Three-Dimensional Character.
作者信息
Cox Brian, Zdorichenko Victor, Cox Philip B, Booker-Milburn Kevin I, Paumier Romain, Elliott Luke D, Robertson-Ralph Michael, Bloomfield Graham
机构信息
School of Life Sciences, University of Sussex, Brighton BN1 9QJ, U.K.
Photodiversity Ltd, c/o School of Life Sciences, University of Sussex, Brighton BN1 9QJ, U.K.
出版信息
ACS Med Chem Lett. 2020 Mar 27;11(6):1185-1190. doi: 10.1021/acsmedchemlett.0c00039. eCollection 2020 Jun 11.
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 sp 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.
摘要
随着化合物失败率的上升，向患者提供新药的压力持续增大，从而使当前的研发模式面临风险。分析表明，增加潜在药物候选物的三维性可降低失败风险，并提高结合选择性和频率。因此，许多研究人员重新审视了光化学的力量，将其作为一种手段来生成用于药物发现计划的富含sp的新型支架。在此，我们报告了一系列具有固有3D特征（PMI和PBF评分）的2,4-亚甲基脯氨酸的设计、合成及计算结构分析，其3D特征显著高于更广泛的艾伯维三规则（Ro3）集合。
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本文引用的文献
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ACS Med Chem Lett. 2019 Oct 22;10(11):1512-1517. doi: 10.1021/acsmedchemlett.9b00409. eCollection 2019 Nov 14.
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