Universität Leipzig, Institut für Organische Chemie, Johannisallee 29, D-04103 Leipzig, Germany.
Rice University, Department of Chemistry, BioScience Research Collaborative, 6500 Main St., Houston, Texas 77030, USA.
Beilstein J Org Chem. 2013 Oct 31;9:2328-35. doi: 10.3762/bjoc.9.267. eCollection 2013.
The chemical synthesis and biological evaluation of new cyclopamine analogs bearing exocyclic methylenes in different positions is described. Bis-exo-cyclopamine 6 was identified as a potent inhibitor of the Gli1-dependent luciferase expression in Shh-LIGHTII cells. An extension of this study to F-ring-modified structures shows the necessity of a rigidly positioned nitrogen atom for bioactivity as well as the presence of the C21 methyl group for acid stability and bioactivity.
描述了具有不同位置外亚甲基的新型沙蟾毒精类似物的化学合成和生物评价。双外消旋环巴胺 6 被鉴定为 Shh-LIGHTII 细胞中Gli1 依赖性荧光素酶表达的有效抑制剂。对 F 环修饰结构的进一步研究表明，生物活性需要刚性定位的氮原子以及 C21 甲基的存在以确保酸稳定性和生物活性。
