申请人:BioMendics, LLC
公开号:US10426742B2
公开(公告)日:2019-10-01
Methods and compounds are disclosed for wound healing by modulating autophagy. A formulation for modulating autophagy comprises a first modulating compound (FAM) selected from compounds having the general structure (I):
wherein: L represents a linker selected from —C≡C—, (a tolan), —CH═CH— (a stilbene, preferably trans); or —CRa═CRb— a stilbene derivative; where Ra and Rb are independently H or phenyl optionally substituted with —(R3)p or —(R4)q;
R1 to R4 are independent substituents at any available position of the phenyl rings, preferably at 3, 3′, 4, 4′, and/or 5, 5′; and m, n, p, and q are independently 0, 1, 2, or 3 representing the number of substituents of the rings, respectively, but at least one of m or n must be ≥1. Each R1 to R2 is independently selected from substituents described herein, including but not limited to hydroxyl, alkoxy, halo, halomethyl and glycosides. The formulation may also include an auxiliary autophagy modulating compound (AAM) as described herein. The formulation may include a hydrogel formed by the compounds themselves or otherwise and may include salts and/or complexes.
本发明公开了通过调节自噬促进伤口愈合的方法和化合物。用于调节自噬的制剂包括选自具有一般结构 (I) 的化合物的第一调节化合物 (FAM):
其中L 代表选自-C≡C-(甲苯)、-CH═CH-(二苯乙烯,最好是反式)或-CRa═CRb-二苯乙烯衍生物的连接体;其中 Ra 和 Rb 独立地是 H 或任选被-(R3)p 或-(R4)q 取代的苯基;
R1至R4是独立的取代基,位于苯基环的任何可用位置,优选位于3,3′、4,4′和/或5,5′;m、n、p和q分别独立地为0、1、2或3,代表环的取代基数目,但m或n中至少有一个必须≥1。每个 R1 至 R2 独立地选自本文所述的取代基,包括但不限于羟基、烷氧基、卤代、卤代甲基和苷。制剂还可包括本文所述的辅助自噬调节化合物(AAM)。制剂可包括由化合物本身或以其它方式形成的水凝胶,并可包括盐和/或复合物。