The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
该描述涉及基于亚
酰亚胺的化合物,包括包含相同亚
酰亚胺基团的双官能化合物,这些化合物作为有针对性的泛素化调节剂具有实用性,尤其是根据本发明的双官能化合物对多种
多肽和其他蛋白质的
抑制剂。特别是,该描述提供了化合物,其中一端包含与cereblon E3泛素连接酶结合的
配体,另一端包含结合目标蛋白质的基团,使目标蛋白质靠近泛素连接酶以实现该蛋白质的降解(和抑制)。可以合成表现出广泛药理活性的化合物,与几乎任何类型的有针对性的
多肽的降解/抑制相一致。