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Abstract：
This work relates to the design and synthesis of a series of novel multi-target directed ligands (MTDLs), i.e., compounds 4a-l, via a convenient one-pot three-component Hantzsch reaction. This approach targeted calcium channel antagonism, antioxidant capacity, cathepsin S inhibition, and interference with Nrf2 transcriptional activation. Of these MTDLs, 4i emerged as a promising compound, demonstrating robust antioxidant activity, the ability to activate Nrf2-ARE pathways, as well as calcium channel blockade and cathepsin S inhibition. Dihydropyridine 4i represents the first example of an MTDL that combines these biological activities.
摘要：
这项工作涉及一系列新型多目标定向配体（MTDL）的设计和合成，即，化合物4a-l,通过方便的一锅三组分Hantzsch反应。这种方法有针对性的钙通道拮抗作用，抗氧化能力，组织蛋白酶S抑制,和干扰Nrf2转录激活。在这些MTDL中，4i成为一种有前途的化合物，表现出强大的抗氧化活性，激活Nrf2-ARE通路的能力，以及钙通道阻断和组织蛋白酶S抑制。二氢吡啶4i代表结合这些生物活性的MTDL的第一个实例。
