A novel branched fluorine-containing compound represented by formula (1):

##STR00001##

wherein L represents a predetermined carbon-containing linker moiety; Rf, in each occurrence, is the same or different and represents fluoroalkyl optionally having at least one ether bond; Y, in each occurrence, is the same or different and represents a predetermined divalent linking group or a bond; R.sup.Y, in each occurrence, is the same or different and represents hydrogen or an organic group; L represents an (n1+n2)-valent carbon-containing linker moiety having at least one carbon atom; n1 represents a number greater than or equal to 1; n2 represents a number greater than or equal to 1; n1+n2 is a number from 3 to 6; X, in each occurrence, is the same or different and represents a divalent linking group or a bond; A, in each occurrence, is the same or different and represents -ArSO.sub.3M or the like; M, in each occurrence, is the same or different and represents hydrogen, —NR.sub.4, or a metal salt; and R represents hydrogen or a C.sub.1-4 organic group.

What is described is a compound of formula (1) ##STR00001##
wherein R.sub.1 and R.sub.2 are the same or different, each a linear or branched alkyl with 1-9 carbons, or an alkenyl or alkynyl with 2 to 11 carbon atoms; L.sub.1 and L.sub.2 are the same or different, each a linear alkyl having 5 to 18 carbon atoms, or form a heterocycle with N; X.sub.1 is a bond, or is —CO—O— whereby L.sub.2-CO—O—R.sub.2 is formed; X.sub.2 is S or O; L.sub.3 is a bond or a lower alkyl, or form a heterocycle with N; R.sub.3 is a lower alkyl; and R.sub.4 and R.sub.5 are the same or different, each a lower alkyl;
or a pharmaceutically acceptable salt thereof.

What is described is a compound of formula (1) ##STR00001##
wherein R.sub.1 and R.sub.2 are the same or different, each a linear or branched alkyl with 1-9 carbons, or an alkenyl or alkynyl with 2 to 11 carbon atoms; L.sub.1 and L.sub.2 are the same or different, each a linear alkyl having 5 to 18 carbon atoms, or form a heterocycle with N; X.sub.1 is a bond, or is —CO—O— whereby L.sub.2-CO—O—R.sub.2 is formed; X.sub.2 is S or O; L.sub.3 is a bond or a lower alkyl, or form a heterocycle with N; R.sub.3 is a lower alkyl; and R.sub.4 and R.sub.5 are the same or different, each a lower alkyl;
or a pharmaceutically acceptable salt thereof.

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.

Provided herein are compounds, pharmaceutical compositions, and methods of treatment for various diseases or conditions, such as cancer. In one aspect, the method comprises the treatment of metastatic cancers. Compounds and methods provided herein are also used for the treatment of diseases such as inflammatory disease, cardiovascular disease, autoimmune disease, and dry eye syndrome. Further provided herein are dietary supplement formulations and methods for supporting a healthy lifestyle.

This invention provides preparations, compositions, products, and applications of photo-crosslinked hydrogels. Component A—a photosensitive polymer derivative, component B—the photoinitiator, and auxiliary component C—other biocompatible polymer derivative each are respectively dissolved in a biocompatible medium to obtain solution A, solution B, and solution C. The solution A, the solution B, and the optional solution C are mixed homogenously to obtain a hydrogel precursor solution. The hydrogel precursor solution is subject to irradiation of the UV light for photocoupled crosslinking to form a photo-crosslinked hydrogel. The photo-crosslinked hydrogel exhibit rapid speed of photo-curing, strong tissue adhesion, excellent mechanical properties, good biocompatibility, and excellent clinical operability. In addition, this invention also provides a kit for making the photo-crosslinked hydrogel, and applications thereof in tissue engineering, regenerative medicine, 3D printing, and as a carrier of cell, protein, or drug.

This invention provides preparations, compositions, products, and applications of photo-crosslinked hydrogels. Component A—a photosensitive polymer derivative, component B—the photoinitiator, and auxiliary component C—other biocompatible polymer derivative each are respectively dissolved in a biocompatible medium to obtain solution A, solution B, and solution C. The solution A, the solution B, and the optional solution C are mixed homogenously to obtain a hydrogel precursor solution. The hydrogel precursor solution is subject to irradiation of the UV light for photocoupled crosslinking to form a photo-crosslinked hydrogel. The photo-crosslinked hydrogel exhibit rapid speed of photo-curing, strong tissue adhesion, excellent mechanical properties, good biocompatibility, and excellent clinical operability. In addition, this invention also provides a kit for making the photo-crosslinked hydrogel, and applications thereof in tissue engineering, regenerative medicine, 3D printing, and as a carrier of cell, protein, or drug.

Provided is a method for amidating a hydroxy ester compound at a high chemical selectivity. The amidation reaction method for a hydroxy ester compound comprises, in the presence of a catalyst containing a compound of a transition metal of the group 4 or group 5 in the periodic table, reacting at least one kind of hydroxy ester compound selected from the group consisting of an -hydroxy ester compound, a -hydroxy ester compound, a -hydroxy ester compound and a -hydroxy ester compound with an amino compound so as to amidate an ester group having a hydroxyl group at the -, -, - or -position of the hydroxy ester compound.

Provided is a method for amidating a hydroxy ester compound at a high chemical selectivity. The amidation reaction method for a hydroxy ester compound comprises, in the presence of a catalyst containing a compound of a transition metal of the group 4 or group 5 in the periodic table, reacting at least one kind of hydroxy ester compound selected from the group consisting of an -hydroxy ester compound, a -hydroxy ester compound, a -hydroxy ester compound and a -hydroxy ester compound with an amino compound so as to amidate an ester group having a hydroxyl group at the -, -, - or -position of the hydroxy ester compound.