The present invention relates to compounds which inhibit histone deacetylase activity and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to methods of treating and preventing hematological cell proliferative disorders, such as multiple myeloma, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The disclosure is directed to, in part, to BCL-2 inhibitors, pharmaceutical compositions comprising the same, as well as methods of their use and preparation.

The disclosure is directed to, in part, to BCL-2 inhibitors, pharmaceutical compositions comprising the same, as well as methods of their use and preparation.

The present disclosure provides a method for preparing a pyrazine compound of formula (I). In the present disclosure, 3-hydroxyl-6-bromopyrazine-2-amide is subjected to a reaction in the presence of phosphorus oxychloride and DIEA, during which adding an organic inorganic chloride makes the content of impurities greatly decreased, thereby obtaining 3,6-dichloropyrazine-2-carbonitrile with high-purity. 3,6-dichloropyrazine-2-carbonitrile prepared in the present disclosure is high in purity, low in production cost and suitable for industrial scale-up production and is very helpful for follow-on production of favipiravir API.

##STR00001##

The present disclosure provides a method for preparing a pyrazine compound of formula (I). In the present disclosure, 3-hydroxyl-6-bromopyrazine-2-amide is subjected to a reaction in the presence of phosphorus oxychloride and DIEA, during which adding an organic inorganic chloride makes the content of impurities greatly decreased, thereby obtaining 3,6-dichloropyrazine-2-carbonitrile with high-purity. 3,6-dichloropyrazine-2-carbonitrile prepared in the present disclosure is high in purity, low in production cost and suitable for industrial scale-up production and is very helpful for follow-on production of favipiravir API.

##STR00001##

Compounds of formula (I), wherein the substituents are as defined in claim 1, and the agrochemically acceptable salts, stereoisomers, enantiomers, tautomers and N-oxides of those compounds, can be used as insecticides.

##STR00001##

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.

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.

Provided herein are Myc-Max inhibitory compounds having the structure of Formula (I) and compositions thereof for use in the treatment of cancer. In particular, the Myc-Max inhibitory compounds may be useful for the treatment of cancers selected from one or more of: prostate cancer, breast cancer, colon cancer, cervical cancer, small-cell lung carcinomas, neuroblastomas, osteosarcomas, glioblastomas, melanoma and myeloid leukaemia.

##STR00001##

Provided herein are Myc-Max inhibitory compounds having the structure of Formula (I) and compositions thereof for use in the treatment of cancer. In particular, the Myc-Max inhibitory compounds may be useful for the treatment of cancers selected from one or more of: prostate cancer, breast cancer, colon cancer, cervical cancer, small-cell lung carcinomas, neuroblastomas, osteosarcomas, glioblastomas, melanoma and myeloid leukaemia.

##STR00001##