Department of Chemistry and Molecular Biology, Medicinal Chemistry, University of Gothenburg, SE-412 96, Göteborg, Sweden.
Department of Chemistry and Molecular Biology, Medicinal Chemistry, University of Gothenburg, SE-412 96, Göteborg, Sweden; Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FIN-00014, Helsinki, Finland.
Eur J Med Chem. 2016 May 23;114:59-64. doi: 10.1016/j.ejmech.2016.02.046. Epub 2016 Feb 21.
A scaffold approach has been used to develop somatostatin β-turn mimetics based on chroman-4-one and chromone ring systems. Such derivatives could adopt conformations resembling type II or type II' β-turns. Side chain equivalents of the crucial Trp8 and Lys9 in somatostatin were introduced in the 2- and 8-positions of the scaffolds using efficient reactions. Interestingly, this proof-of-concept study shows that 4 and 9 have Ki-values in the low μM range when evaluated for their affinity for the sst2 and sst4 receptors.
一种支架方法已被用于开发基于色满-4-酮和色酮环系统的生长抑素β-转角类似物。此类衍生物可以采用类似于 II 型或 II'型β-转角的构象。使用有效的反应，在支架的 2-和 8-位引入生长抑素中关键的色氨酸 8 和赖氨酸 9 的侧链等价物。有趣的是，这项概念验证研究表明，当评估它们对 sst2 和 sst4 受体的亲和力时，4 和 9 的 Ki 值在低 μM 范围内。
