Wang Xiaoyun, He Jieyu, Hosseini-Gerami Layla, Thomas Morgan, Thompson Stephen, Ford Joseph, Ortalli Sebastiano, Chen Zijun, Destro Gianluca, Bender Andreas, Aigbirhio Franklin, Gouverneur Véronique
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, U.K.
J Org Chem. 2025 Aug 1;90(30):10941-10947. doi: 10.1021/acs.joc.5c00918. Epub 2025 Jul 21.
The angiotensin-converting enzyme 2 (ACE2) is pivotal as the cellular receptor for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus responsible for COVID-19. This study presents a novel synthetic route for four analogues of MLN-4760, a known inhibitor of ACE2, guided by docking predictions. These synthetic advances enabled in vitro pIC assays confirming the inhibitory potency of the synthesized analogues. Lastly, this route was applied to the synthesis of novel F-labeled ACE2 inhibitors for PET imaging applications.
血管紧张素转换酶2（ACE2）作为严重急性呼吸综合征冠状病毒2（SARS-CoV-2，即导致COVID-19的病毒）的细胞受体至关重要。本研究在对接预测的指导下，为已知的ACE2抑制剂MLN-4760的四种类似物提出了一种新的合成路线。这些合成进展使得能够通过体外pIC测定来确认合成类似物的抑制效力。最后，该路线被应用于合成用于正电子发射断层扫描（PET）成像应用的新型F标记的ACE2抑制剂。
