Odena Carlota, Santiago Tomás G, Linares María Lourdes, Castellanos-Blanco Nahury, McGuire Ryan T, Chaves-Arquero Belén, Alonso Jose Manuel, Diéguez-Vázquez Alejandro, Tan Eric, Alcázar Jesús, Buijnsters Peter, Cañellas Santiago, Martin Ruben
Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Avenida Països Catalans 16, 43007 Tarragona, Spain.
Departament de Química Orgànica, Universitat Rovira i Virgili, c/Marcel·lí Domingo 1, 43007 Tarragona, Spain.
J Am Chem Soc. 2024 Aug 7;146(31):21264-21270. doi: 10.1021/jacs.4c08404. Epub 2024 Jul 25.
Herein, we describe nickel oxidative addition complexes (Ni-OACs) of drug-like molecules as a platform to rapidly generate lead candidates with enhanced C() fraction. The potential of Ni-OACs to access new chemical space has been assessed not only in C()-C() couplings but also in additional bond formations without recourse to specialized ligands and with improved generality when compared to Ni-catalyzed reactions. The development of an automated diversification process further illustrates the robustness of Ni-OACs, thus offering a new gateway to expedite the design-make-test-analyze (DMTA) cycle in drug discovery.
在此，我们将类药物分子的镍氧化加成络合物（Ni - OACs）描述为一个平台，用于快速生成具有更高C()分数的潜在先导化合物。Ni - OACs进入新化学空间的潜力不仅在C() - C()偶联反应中得到评估，而且在其他键形成反应中也得到评估，与镍催化反应相比，无需使用特殊配体且具有更高的通用性。自动化多样化过程的发展进一步说明了Ni - OACs的稳健性，从而为加快药物发现中的设计 - 制造 - 测试 - 分析（DMTA）循环提供了一条新途径。
