Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
Proc Natl Acad Sci U S A. 2021 Jul 13;118(28). doi: 10.1073/pnas.2108881118.
The development of a versatile platform for the synthesis of 1,2-difunctionalized bicyclo[1.1.1]pentanes to potentially mimic /-substituted arenes is described. The syntheses of useful building blocks bearing alcohol, amine, and carboxylic acid functional handles have been achieved from a simple common intermediate. Several and -substituted benzene analogs, as well as simple molecular matched pairs, have also been prepared using this platform. The results of in-depth ADME (absorption, distribution, metabolism, and excretion) investigations of these systems are presented, as well as computational studies which validate the or -character of these bioisosteres.
描述了一种多功能平台的开发，用于合成 1,2-二官能化双环[1.1.1]戊烷，以潜在模拟 /-取代芳烃。已经从简单的共同中间体中实现了带有醇、胺和羧酸官能团的有用构建块的合成。还使用该平台制备了几种 和 -取代苯类似物以及简单的分子匹配对。提出了对这些系统进行深入的 ADME（吸收、分布、代谢和排泄）研究的结果，以及计算研究，这些研究验证了这些生物等排体的 或 -特性。
