Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.

A composition comprising a polyphenol compound (B), wherein the polyphenol compound (B) is one or more selected from the group consisting of a compound represented by the following formula (1) and a resin having a structure represented by the following formula (2):

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Methods for making prodrugs of treprostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 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.

Methods for making prodrugs of treprostinil and treprostinil derivatives are provided. Specifically, methods are provided herein for producing prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 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.

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Prostacyclin compounds and compositions comprising the same are provided herein. Specifically, prostacyclin compounds comprising treprostinil covalently linked to a linear C.sub.5-C.sub.18 alkyl, branched C.sub.5-C.sub.18 alkyl, linear C.sub.2-C.sub.18 alkenyl, branched C.sub.3-C.sub.18 alkenyl, aryl, aryl-C.sub.1-C.sub.18 alkyl or an amino acid or a peptide (e.g., dipeptide, tripeptide, tetrapeptide) are described. The linkage, in one embodiment, is via a carbamate, amide or ester bond. Prostacyclin compounds provided herein can also include at least one hydrogen atom substituted with at least one deuterium atom. Methods for treating pulmonary hypertension (e.g., pulmonary arterial hypertension) and portopulmonary hypertension are also provided.

Provided is a method for producing a chlorophenoxycarboxylate, comprising the following steps of: a phenoxycarboxylate under actions of a catalyst A and a catalyst B performing a selective chlorination of a chlorinating agent at a 2-position and/or a 4-position to obtain the chlorophenoxycarboxylate; the catalyst A is a Lewis acid; and the catalyst B has the following structure: R.sub.1′—S—R.sub.2′. The present disclosure redesigns the process route, and finely screens the catalyst and the chlorinating agent, thereby effectively improving the chlorination selectivity while avoiding the loss of the active ingredient, and the content of the obtained chlorophenoxycarboxylate can reach more than 98.5%, and the yield can reach more than 99%.

Provided is a method for producing a chlorophenoxycarboxylate, comprising the following steps of: a phenoxycarboxylate under actions of a catalyst A and a catalyst B performing a selective chlorination of a chlorinating agent at a 2-position and/or a 4-position to obtain the chlorophenoxycarboxylate; the catalyst A is a Lewis acid; and the catalyst B has the following structure: R.sub.1′—S—R.sub.2′. The present disclosure redesigns the process route, and finely screens the catalyst and the chlorinating agent, thereby effectively improving the chlorination selectivity while avoiding the loss of the active ingredient, and the content of the obtained chlorophenoxycarboxylate can reach more than 98.5%, and the yield can reach more than 99%.

Compounds represented by formulae I, II, III, and IV including pro-drugs for treprostinil and prostacyclin analogs. Uses include treatment of pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH). The structures of the compounds can be adapted to the particular application for a suitable treatment dosage. Transdermal applications can be used.