Novel crystalline forms of Treprostinil monohydrate, a mixture including the same, and preparation methods thereof.

Novel crystalline forms of Treprostinil monohydrate, a mixture including the same, and preparation methods thereof.

A radiation-sensitive resin composition contains: a polymer having an acid-labile group, a radiation-sensitive acid generator, a compound represented by the following formula (1), and a solvent. In the formula (1), X represents an oxygen atom or a sulfur atom; R.sup.1 represents a hydrogen atom or a monovalent organic group having 1 to 20 carbon atoms; R.sup.2 to R.sup.5 each independently represent a hydrogen atom or a monovalent organic group having 1 to 20 carbon atoms, and optionally two or more of R.sup.2 to R.sup.5 taken together represent an alicyclic structure having 3 to 20 ring atoms or an aliphatic heterocyclic structure having 3 to 20 ring atoms together with the carbon atom to which the two or more of R.sup.2 to R.sup.5 bond; Z.sup.n+ represents a cation having a valency of n; and n is an integer of 1 to 3. ##STR00001##

A radiation-sensitive resin composition contains: a polymer having an acid-labile group, a radiation-sensitive acid generator, a compound represented by the following formula (1), and a solvent. In the formula (1), X represents an oxygen atom or a sulfur atom; R.sup.1 represents a hydrogen atom or a monovalent organic group having 1 to 20 carbon atoms; R.sup.2 to R.sup.5 each independently represent a hydrogen atom or a monovalent organic group having 1 to 20 carbon atoms, and optionally two or more of R.sup.2 to R.sup.5 taken together represent an alicyclic structure having 3 to 20 ring atoms or an aliphatic heterocyclic structure having 3 to 20 ring atoms together with the carbon atom to which the two or more of R.sup.2 to R.sup.5 bond; Z.sup.n+ represents a cation having a valency of n; and n is an integer of 1 to 3. ##STR00001##

An onium salt having formula (1) serving as an acid diffusion inhibitor and a chemically amplified resist composition comprising the acid diffusion inhibitor are provided. When processed by lithography, the resist composition forms a pattern having minimal defects and excellent lithography performance factors such as CDU, LWR and DOF.

##STR00001##

A phenoxy carboxylic acid compound, its pharmaceutically acceptable salt or ester, stereoisomer, prodrug, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof; a pharmaceutical composition comprising the compound, its pharmaceutically acceptable salt or ester, stereoisomer, prodrug, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof; and a medicinal use of the compound, its pharmaceutically acceptable salt or ester, stereoisomer, prodrug, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof, for preventing and/or treatment of a metabolic disease (e.g., metabolic syndrome, non-alcoholic fatty liver disease, and/or diabetes mellitus).

A phenoxy carboxylic acid compound, its pharmaceutically acceptable salt or ester, stereoisomer, prodrug, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof; a pharmaceutical composition comprising the compound, its pharmaceutically acceptable salt or ester, stereoisomer, prodrug, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof; and a medicinal use of the compound, its pharmaceutically acceptable salt or ester, stereoisomer, prodrug, hydrate, solvate or crystal form, or metabolite form thereof, or any combination or mixture thereof, for preventing and/or treatment of a metabolic disease (e.g., metabolic syndrome, non-alcoholic fatty liver disease, and/or diabetes mellitus).

A method for the synthesis of specialized pro-resolving mediators, structural isomers thereof and analogs thereof is disclosed herein. The method comprises reacting a compound of the formula (I):

##STR00001## wherein R.sub.1 is alkyl.sub.(C≤12), cycloalkyl.sub.(C≤12), alkenyl.sub.(C≤12), alkylidene.sub.(C≤12), alkynyl.sub.(C≤12), aryl, aralkyl, heteroaryl or heteroaralkyl; and X.sub.1, X.sub.2 and X.sub.3 are each independently hydroxy or OP, wherein P is a hydroxy protecting or hydroxy activating group; with a reducing agent under conditions sufficient to produce a compound of the formula (II):

##STR00002## wherein: R.sub.1, X.sub.1, X.sub.2 and X.sub.3 are as defined above.

Novel protectins, more specifically novel structural isomers and analogs of PD1 and PDX are also disclosed.

A method for the synthesis of specialized pro-resolving mediators, structural isomers thereof and analogs thereof is disclosed herein. The method comprises reacting a compound of the formula (I):

##STR00001## wherein R.sub.1 is alkyl.sub.(C≤12), cycloalkyl.sub.(C≤12), alkenyl.sub.(C≤12), alkylidene.sub.(C≤12), alkynyl.sub.(C≤12), aryl, aralkyl, heteroaryl or heteroaralkyl; and X.sub.1, X.sub.2 and X.sub.3 are each independently hydroxy or OP, wherein P is a hydroxy protecting or hydroxy activating group; with a reducing agent under conditions sufficient to produce a compound of the formula (II):

##STR00002## wherein: R.sub.1, X.sub.1, X.sub.2 and X.sub.3 are as defined above.

Novel protectins, more specifically novel structural isomers and analogs of PD1 and PDX are also disclosed.

The present disclosure provides treprostinil derivatives that can act as prodrugs of treprostinil. The treprostinil derivatives can be used to treat any conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.