Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, Germany.
Arch Pharm (Weinheim). 2022 Aug;355(8):e2200111. doi: 10.1002/ardp.202200111. Epub 2022 May 4.
Amine oxidase copper containing 3 (AOC3), also known as plasma amine oxidase, semicarbazide-sensitive amine oxidase, or vascular adhesion protein-1, catalyzes the oxidative deamination of primary amines to aldehydes using copper and a quinone as cofactors. Because it is involved in the transmigration of inflammatory cells through blood vessels into tissues, AOC3 is thought to play an important role in inflammatory diseases. Therefore, inhibitors of this enzyme could lead to new therapeutics for the treatment of inflammation-related diseases. Recently, 6-(5-phenyl-2H-tetrazol-2-yl)hexan-1-amine was found to be a tight-binding substrate of AOC3. To obtain novel inhibitors of the enzyme, the amino group of this substrate was replaced with functional groups that occur in known AOC3 inhibitors, such as hydrazide or glycine amide moieties. In addition, derivatives of the compounds obtained in this way were prepared. The obtained hydrazide 5, which proved to be the most effective, was subjected to further structural modifications. Selected hydrazides were evaluated for selectivity toward some other amine oxidases.
含铜胺氧化酶 3（AOC3），也称为血浆胺氧化酶、半卡巴肼敏感胺氧化酶或血管黏附蛋白 1，使用铜和醌作为辅助因子，催化伯胺的氧化脱氨为醛。由于它参与炎症细胞穿过血管迁移到组织中，因此 AOC3 被认为在炎症性疾病中发挥重要作用。因此，该酶的抑制剂可能为治疗与炎症相关的疾病提供新的治疗方法。最近，发现 6-(5-苯基-2H-四唑-2-基)己-1-胺是 AOC3 的紧密结合底物。为了获得该酶的新型抑制剂，将该底物的氨基用在已知 AOC3 抑制剂中出现的官能团取代，如酰肼或甘氨酰胺部分。此外，还制备了以这种方式获得的化合物的衍生物。已证明最有效的获得的酰肼 5 进一步进行结构修饰。对选定的酰肼进行了对其他一些胺氧化酶的选择性评估。
