四取代烷基硫代亚咪唑的多样化和通用的区域选择性合成作为 p38α 丝裂原活化蛋白激酶抑制剂。
A Diverse and Versatile Regiospecific Synthesis of Tetrasubstituted Alkylsulfanylimidazoles as p38α Mitogen-Activated Protein Kinase Inhibitors.
机构信息
Institute of Pharmaceutical Sciences, Department of Medicinal and Pharmaceutical Chemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
Teva-ratiopharm, Graf-Arco-Str. 3, 89079 Ulm, Germany.
出版信息
Molecules. 2018 Jan 20;23(1):221. doi: 10.3390/molecules23010221.
An alternative strategy for the synthesis of 1-aryl- and 1-alkyl-2-methylsulfanyl-4-(4-fluorophenyl)-5-(pyridin-4-yl)imidazoles as potential p38α mitogen-activated protein kinase inhibitors is reported. The regioselective -substitution of the imidazole ring was achieved by treatment of α-aminoketones with different aryl or alkyl isothiocyanates. In contrast to previously published synthesis routes starting from 2-amino-4-methylpyridine, the presented route is characterized by a higher flexibility and a lower number of steps. This strategy was also applied to access 1-alkyl-2-methylsulfanyl-5-(4-fluorophenyl)-4-(pyridin-4-yl)imidazoles in six steps starting from 2-chloro-4-methylpyridine.
报道了一种合成 1-芳基和 1-烷基-2-甲硫基-4-(4-氟苯基)-5-(吡啶-4-基)咪唑的替代策略，这些化合物可能是 p38α 丝裂原活化蛋白激酶抑制剂。通过用不同的芳基或烷基异硫氰酸酯处理α-氨基酮，实现了咪唑环的区域选择性取代。与以前从 2-氨基-4-甲基吡啶开始的发表的合成路线相比，所提出的路线具有更高的灵活性和更少的步骤。该策略还应用于从 2-氯-4-甲基吡啶出发，经过六步反应合成 1-烷基-2-甲硫基-5-(4-氟苯基)-4-(吡啶-4-基)咪唑。
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