公开(公告)号：US20230250051A1

公开(公告)日：2023-08-10

申请号：US18302682

申请日：2023-04-18

申请人： Insmed Incorporated

发明人： Vladimir MALININ ,  Walter PERKINS ,  Fraziska LEIFER ,  Donna M. KONICEK ,  Zhili LI ,  Adam PLAUNT

IPC分类号： C07C231/02 ,  C07C67/08

CPC分类号： C07C231/02 ,  C07C67/08 ,  C07C2602/24 ,  C07C2601/18

摘要： 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-C18alkenyl, branched C3-C18alkenyl, 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.