The present invention relates to a method for the metal-free preparation of a biaryl compound by a photosplicing reaction and its use in the preparation of chemical compounds, preferably of active ingredients e.g. in the fields of pharmaceuticals and agrochemicals. In particular, it refers to a method for the regiocontrolled preparation of a biaryl compound of formula (I): Ar—Ar′ by photochemically reacting a precursor compound of formula (II): Ar—L—Ar′ to form a biaryl compound of general formula: Ar—L—Ar′(II).fwdarw.Ar—Ar′ (I) wherein Ar and Ar′, independently of each other, represent an unsubstituted or substituted C6-C20 aryl group or a heteroaryl group with 5-20 ring atoms selected from carbon, nitrogen, oxygen and sulfur, and L represents a group —X—Y—Z— as defined herein. The biaryl compounds are generally suitable as intermediates or key building blocks in a very broad spectrum of organic chemical syntheses and their respective utilities. Their use within the field of synthesis of active ingredients is an aspect of the invention, and their use in the preparation of pharmaceutically active ingredients is particularly preferred.

Provided herein are arylcyclopropyl amino-isoquinoline amide compounds. In particular, the disclosure provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the disclosure are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, diseases characterized by abnormal growth, such as cancers, and inflammatory diseases. The disclosure further provides compositions containing isoquinoline amide compounds.

Provided herein are arylcyclopropyl amino-isoquinoline amide compounds. In particular, the disclosure provides compounds that affect the function of kinases in a cell and that are useful as therapeutic agents or with therapeutic agents. The compounds of the disclosure are useful in the treatment of a variety of diseases and conditions including eye diseases such as glaucoma, cardiovascular diseases, diseases characterized by abnormal growth, such as cancers, and inflammatory diseases. The disclosure further provides compositions containing isoquinoline amide compounds.

The present invention relates to a method for preparing 2-(2,5-difluorophenyl)-3-carboxy-7-chloro-(4H)-4-benzopyranone represented by formula 1 below, a novel intermediate used therein, and a method for preparing the same. Specifically, an object of the present invention is to provide a novel preparation method, in which the compound of formula 1 below can be efficiently and economically synthesized and can be mass-produced in a high yield.

##STR00001##

The object of the present invention is to provide a mitochondrial dysfunction improving agent comprising a vitamin K derivative having a high deliverability to mitochondria.

A mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising at least one of a carboxylic acid ester of an active vitamin K represented by a general formula (1) or a salt thereof, and

##STR00001##

(wherein, R.sub.1 and R.sub.2 are a hydrogen atom, respectively, or a substituent selected from glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof; and at least either of R.sub.1 and R.sub.2 is glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof. R.sub.3 is a group represented by a general formula (2), or a general formula (3). n is an integer of 1 to 7)

##STR00002##

a mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising a carboxylic acid ester of an active vitamin K or a salt thereof (in the general formula (1), R.sub.1 and R.sub.2 is a carboxylic acid residue selected from a group consisting of R.sub.4OOCCH.sub.2CH.sub.2CO— and R.sub.4OOCCH.sub.2CH.sub.2CH.sub.2CO—. R.sub.3 represents the above general formula (2) or (3). R.sub.4 is a C1-C3 alkyl group.).

The object of the present invention is to provide a mitochondrial dysfunction improving agent comprising a vitamin K derivative having a high deliverability to mitochondria.

A mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising at least one of a carboxylic acid ester of an active vitamin K represented by a general formula (1) or a salt thereof, and

##STR00001##

(wherein, R.sub.1 and R.sub.2 are a hydrogen atom, respectively, or a substituent selected from glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof; and at least either of R.sub.1 and R.sub.2 is glycine, N-acyl glycine, N-alkyl glycine, N,N-dialkyl glycine, N,N,N-trialkyl glycine, acyl, dicarboxylic acid hemiester, and salts thereof. R.sub.3 is a group represented by a general formula (2), or a general formula (3). n is an integer of 1 to 7)

##STR00002##

a mitochondrial dysfunction improving agent, neurodegeneration improving agent, amyotrophic lateral sclerosis improving agent, Alzheimer's disease improving agent, and Parkinson's disease improving agent comprising a carboxylic acid ester of an active vitamin K or a salt thereof (in the general formula (1), R.sub.1 and R.sub.2 is a carboxylic acid residue selected from a group consisting of R.sub.4OOCCH.sub.2CH.sub.2CO— and R.sub.4OOCCH.sub.2CH.sub.2CH.sub.2CO—. R.sub.3 represents the above general formula (2) or (3). R.sub.4 is a C1-C3 alkyl group.).

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): ##STR00001##
or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein n, x, A, Q.sub.1, Q.sub.2, Z, R, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined herein. Pharmaceutical compositions containing such compounds, as well as to compounds themselves, are also provided.

The present invention aims to provide a polymerizable compound that has high storage stability without causing crystal precipitation when added to a polymerizable composition and to provide a polymerizable composition containing the polymerizable compound. A polymer film produced by polymerization of the polymerizable composition has a low haze, high thickness uniformity, low occurrence of nonuniform orientation, high surface hardness, high adhesiveness, and good appearances and fewer orientation defects even after ultraviolet irradiation. The present invention also aims to provide a polymer produced by polymerization of the polymerizable composition and an optically anisotropic body produced from the polymer.

The present invention aims to provide a polymerizable compound that has high storage stability without causing crystal precipitation when added to a polymerizable composition and to provide a polymerizable composition containing the polymerizable compound. A polymer film produced by polymerization of the polymerizable composition has a low haze, high thickness uniformity, low occurrence of nonuniform orientation, high surface hardness, high adhesiveness, and good appearances and fewer orientation defects even after ultraviolet irradiation. The present invention also aims to provide a polymer produced by polymerization of the polymerizable composition and an optically anisotropic body produced from the polymer.

Methods for rapid, efficient, and safe fluoridation and radiolabeling of established and new biomarkers are described. More specifically, the described herein methods may be used for fluoridation of biomarkers or to facilitate isotopic exchanges, especially .sup.19F/.sup.18F IEX, for rapid and efficient manufacturing of radiotracers, including radiotracers for positron emission tomography (PET), under clinically relevant conditions.