Methods of manufacturing treprostinil and treprostinil derivative prodrugs

US10343979B2 · kind B2 · utility

Assignee

• Insmed Incorporated · US

Inventors

• Vladimir Malinin · Bound Brook Junction, US
• Walter Perkins · Ewing Township, US
• Franziska Leifer · Bound Brook, US
• Donna Konicek · Montgomery, US
• Zhili Li · Bound Brook, US
• Adam Plaunt · Phillipsburg, US

Key dates

• Filing date: Nov 18, 2015
• Grant date: Jul 9, 2019
• Expiry date: Nov 18, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C2602/24
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

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.