Substituted aromatic sulfonamides of formula (I)

##STR00001##

pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease.

The present invention provides a novel process for preparing the compound I containing the compound [I(A)] (vadadustat) and the compound [I(B)] (roxadustat) which are useful as a medicine in an industrially advantageous manner, and a process for preparing the compound I which comprises reacting the compound (a1) or the compound (b1), the compound (2) or salts of the compound (2), with carbon monoxide in the presence of a palladium catalyst, in the presence or absence of a ligand, in the presence of a base, in a solvent to prepare the compound I (wherein structure formulae of the compound (a1), the compound (b1) or the compound (2), and the definitions of groups in the formulae are defined in the Description).

##STR00001##

The present invention provides a novel process for preparing the compound I containing the compound [I(A)] (vadadustat) and the compound [I(B)] (roxadustat) which are useful as a medicine in an industrially advantageous manner, and a process for preparing the compound I which comprises reacting the compound (a1) or the compound (b1), the compound (2) or salts of the compound (2), with carbon monoxide in the presence of a palladium catalyst, in the presence or absence of a ligand, in the presence of a base, in a solvent to prepare the compound I (wherein structure formulae of the compound (a1), the compound (b1) or the compound (2), and the definitions of groups in the formulae are defined in the Description).

##STR00001##

The invention provides compounds of Formula (I), or pharmaceutically acceptable salts 5 thereof:

##STR00001##

The compounds, compositions, methods and kits of the invention are useful for the treatment of pain, cough, itch, and neurogenic inflammation.

The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

The present inventors found cyclic peptide compounds that interact with Ras, and non-natural amino acids useful for the production of the cyclic peptide compounds. The inventors also found that the cyclic peptide compounds inhibit the binding between Ras and SOS. In addition, the inventors found specific non-natural amino acids contained in the cyclic peptide compounds and methods for production thereof.

Provided herein are compounds and their pharmaceutically acceptable salts, lipid particles comprising such compounds or pharmaceutically acceptable salts thereof and compositions of the foregoing that can be used to reduce immune intolerance in a subject, for example, to treat autoimmune disorders, or in combination with an antigenic therapy, such as a protein or gene therapy, to improve the efficacy of the antigenic therapy. The compounds have the following structural formula: ##STR00001##
wherein values for the variables (e.g., Ring A, L, R.sup.1, R.sup.2, R.sup.3, m) are as described herein.

Provided herein are compounds and their pharmaceutically acceptable salts, lipid particles comprising such compounds or pharmaceutically acceptable salts thereof and compositions of the foregoing that can be used to reduce immune intolerance in a subject, for example, to treat autoimmune disorders, or in combination with an antigenic therapy, such as a protein or gene therapy, to improve the efficacy of the antigenic therapy. The compounds have the following structural formula: ##STR00001##
wherein values for the variables (e.g., Ring A, L, R.sup.1, R.sup.2, R.sup.3, m) are as described herein.

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 relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and their use for the treatment of cancer.