Benzimidazole compounds differentiate a mammalian stem cell into mesodermal or cardiomyocyte cells
申请人:Mercola Mark
公开号:US09012217B2
公开(公告)日:2015-04-21
Methods and small molecule compounds for stem cell differentiation are provided. One example of a class of compounds that may be used is represented by the compound having the structure IA or IB in the form of free base or a pharmaceutically acceptable salt, hydrate, solvate or N-oxide thereof:
R1 is independently hydrogen or (C1-C6)alkyl; R2 is independently hydrogen, (C1-C6)alkyl, aryl, or heteroaryl; R2′ is independently hydrogen, (C1-C6)alkyl, CF3 or C2F5; R3 is independently (C1-C6)alkyl, aryl, 2-tetrahydrofurylmethyl, an aliphatic tertiary amine, or 4-methoxybenzyl; or R2 and R3 may be joined together to form a 5 or 6 member ring lactone; R4 is independently hydrogen, (C1-C6)alkyl, a 2- or 4-R5-substituted aromatic ring selected from a 4-R5-phenyl or a 2-R5-5-pyridyl, aryl, heteroaryl, aliphatic tertiary amine or halogen; and R5, R5′, R6, R6′, R7, R7′, are each independently hydrogen, (C1-C6)alkyl, aryl, optionally substituted phenyl, heteroaryl, a heterocyclic ring, an aliphatic tertiary amine, or halogen.
本发明提供了用于干细胞分化的方法和
小分子化合物。可以使用的化合物类别之一的一个示例由IA或IB结构的化合物代表,其为自由碱基或其药学上可接受的盐,
水合物,溶剂合物或N-
氧化物形式:R1独立地为
氢或(C1-C6)烷基;R2独立地为
氢,(C1-C6)烷基,芳基或杂环芳基;R2'独立地为
氢,(C1-C6)烷基,
CF3或
C2F5;R3独立地为(C1-C6)烷基,芳基,2-
四氢呋喃甲基,
脂肪族三级胺或
4-甲氧基苄基;或R2和R3可以结合在一起形成5或6成员环内
酯;R4独立地为
氢,(C1-C6)烷基,2-或4-R5-取代芳香环,所选的芳基环为4-R5-
苯基或2-R5-5-
吡啶基,芳基,杂环芳基,
脂肪族三级胺或卤素;R5,R5',R6,R6',R7,R7'各自独立地为
氢,(C1-C6)烷基,芳基,可选取代的
苯基,杂环芳基,杂环环,
脂肪族三级胺或卤素。