申请人:Insmed Incorporated
公开号:EP3904326A1
公开(公告)日:2021-11-03
Methods for making prodrugs of trepreostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C5-C18 alkyl, branched C5-C18 alkyl, linear C2-C18 alkenyl, branched C3-C18 alkenyl, aryl, aryl-C1-C18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide). The linkage, in one embodiment, is via an amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. The compounds provided herein can be used to treat pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension.
本文提供了曲普瑞替尼和曲普瑞替尼衍生物原药的制备方法。具体而言,本文提供了生产前列环素化合物的方法,该化合物包含与线性 C5-C18 烷基、支链 C5-C18 烷基、线性 C2-C18 烯基、支链 C3-C18 烯基、芳基、芳基-C1-C18 烷基或氨基酸或肽(如二肽、三肽、四肽)共价连接的曲普瑞替尼。在一个实施方案中,连接是通过酰胺键或酯键。本文提供的前列环素化合物还可以包括至少一个被至少一个氘原子取代的氢原子。本文提供的化合物可用于治疗肺动脉高压(如肺动脉高压)和门肺动脉高压。