Compounds that inhibit Myeloid Cell Leukemia-1 (Mcl-1) oncoprotein, and methods of using the same, are provided for treating disease.

The present invention relates to novel compounds of general Formula II:

##STR00001##

wherein the groups X, and R.sup.1 to R.sup.4 have the meanings given in the description, to a process for preparing these compounds and to their use for treating, preventing or ameliorating viral infections and diseases which are associated with PLA2G16.

The present invention relates to novel compounds of general Formula II:

##STR00001##

wherein the groups X, and R.sup.1 to R.sup.4 have the meanings given in the description, to a process for preparing these compounds and to their use for treating, preventing or ameliorating viral infections and diseases which are associated with PLA2G16.

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X—Y is —NHSO.sub.2— or —SO.sub.2NH—; Z is a monocyclic aryl or heteroaryl group, each of which is optionally substituted by one or more substituents selected from alkyl, cycloalkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, C land alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, SO.sub.2NR.sub.12R.sub.13, heteroaryl, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; and R.sub.9 is H, alkyl or halo; R.sub.10 and R.sub.11 are each independently H or alkyl; and R.sub.12 and R.sub.13 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immuno-oncology and related applications. Another aspect of the invention relates to compounds of formulae (la) and (lb).

##STR00001##

The present invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or hydrate thereof, wherein: the group X—Y is —NHSO.sub.2— or —SO.sub.2NH—; Z is a monocyclic aryl or heteroaryl group, each of which is optionally substituted by one or more substituents selected from alkyl, cycloalkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.1 is H or alkyl; R.sub.2 is selected from COOH and a tetrazolyl group; R.sub.3 is selected from H, C land alkyl; R.sub.4 is selected from H and halo; R.sub.5 is selected from H, alkyl, haloalkyl, SO.sub.2-alkyl, Cl, alkoxy, OH, CN, hydroxyalkyl, alkylthio, heteroaryl, cycloalkyl, heterocycloalkyl and haloalkoxy; R.sub.6 is H; R.sub.7 is selected from H, CN, haloalkyl, halo, SO.sub.2-alkyl, SO.sub.2NR.sub.12R.sub.13, heteroaryl, CONR.sub.10R.sub.11 and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R.sub.8 is selected from H, alkyl, haloalkyl and halo; and R.sub.9 is H, alkyl or halo; R.sub.10 and R.sub.11 are each independently H or alkyl; and R.sub.12 and R.sub.13 are each independently H or alkyl. Further aspects of the invention relate to such compounds for use in the field of immuno-oncology and related applications. Another aspect of the invention relates to compounds of formulae (la) and (lb).

##STR00001##

Compounds of Formula (I) or (X) are provided including for treatment of disorders such as a disorder or symptom associated with neuronal cell death. In one aspect, compounds which are selective inhibitors of calpain-2 are provided. Preferred compounds can be useful to treat acute neurodegeneration.

This disclosure is related to aromatic compounds of formula (I), and methods of their use in treating medical conditions associated with Heat Shock Protein-90 (HSP90), e.g., cancer. Compounds of formula (I) have the following structure: ##STR00001##
Also disclosed are pharmaceutical compositions comprising compounds of formula (I).

Disclosed are HPTS series derivatives and a synthesis method thereof, belonging to the field of organic synthesis. The HPTS series derivatives are prepared by introducing alkylamine or alcohol into sulfonic acid groups of HPTS. The synthesis method comprises the following steps: subjecting HPTS and phosphorus oxychloride to heating and reflux reaction for 12 hours under catalysis of DMF to obtain a reaction product; introducing the reaction product into ice water, stirring, precipitating solid, and performing suction filtration to obtain HPTS-SO.sub.2Cl; dissolving the HPTS-SO.sub.2Cl in tetrahydrofuran to prepare solution A, and dissolving alkylamine or alcohol in tetrahydrofuran to prepare solution B; mixing the solution A with the solution B and then reacting for 24 hours at normal temperature, obtaining a product by rotary evaporation, and obtaining a pure compound after separation through columns. The derivatives have strong fat solubility, overcome the defect of a very strong water solubility.

Disclosed are HPTS series derivatives and a synthesis method thereof, belonging to the field of organic synthesis. The HPTS series derivatives are prepared by introducing alkylamine or alcohol into sulfonic acid groups of HPTS. The synthesis method comprises the following steps: subjecting HPTS and phosphorus oxychloride to heating and reflux reaction for 12 hours under catalysis of DMF to obtain a reaction product; introducing the reaction product into ice water, stirring, precipitating solid, and performing suction filtration to obtain HPTS-SO.sub.2Cl; dissolving the HPTS-SO.sub.2Cl in tetrahydrofuran to prepare solution A, and dissolving alkylamine or alcohol in tetrahydrofuran to prepare solution B; mixing the solution A with the solution B and then reacting for 24 hours at normal temperature, obtaining a product by rotary evaporation, and obtaining a pure compound after separation through columns. The derivatives have strong fat solubility, overcome the defect of a very strong water solubility.

Disclosed are HPTS series derivatives and a synthesis method thereof, belonging to the field of organic synthesis. The HPTS series derivatives are prepared by introducing alkylamine or alcohol into sulfonic acid groups of HPTS. The synthesis method comprises the following steps: subjecting HPTS and phosphorus oxychloride to heating and reflux reaction for 12 hours under catalysis of DMF to obtain a reaction product; introducing the reaction product into ice water, stirring, precipitating solid, and performing suction filtration to obtain HPTS-SO.sub.2Cl; dissolving the HPTS-SO.sub.2Cl in tetrahydrofuran to prepare solution A, and dissolving alkylamine or alcohol in tetrahydrofuran to prepare solution B; mixing the solution A with the solution B and then reacting for 24 hours at normal temperature, obtaining a product by rotary evaporation, and obtaining a pure compound after separation through columns. The derivatives have strong fat solubility, overcome the defect of a very strong water solubility.