申请人:Arvinas, Inc.
公开号:US20160058872A1
公开(公告)日:2016-03-03
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。