This invention relates to methods for treating bone disease associated with osteoclast activation using HDAC6 selective inhibitors, e.g., small molecule inhibitors such as reverse amide compounds.

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure:

##STR00001##

wherein A is an aryl or heteroaryl, each with or without subsutitution; and R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.7, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising: (a) reacting a compound having the structure:

##STR00002##

with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:

##STR00003##

and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

##STR00004##

The present invention provides a process of producing a trifluoromethoxylated aryl or trifluoromethoxylated heteroaryl having the structure:

##STR00001##

wherein A is an aryl or heteroaryl, each with or without subsutitution; and R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.7, —NH-(alkenyl), —NH-(alkynyl) —NH-(aryl), —NH-(heteroaryl), —O-(alkyl), —O-(alkenyl), —O-(alkynyl), —O-(aryl), —O-(heteroaryl), —S-(alkyl), —S-(alkenyl), —S-(alkynyl), —S-(aryl), or —S-(heteroaryl), comprising: (a) reacting a compound having the structure:

##STR00002##

with a trifluoromethylating agent in the presence of a base in a first suitable solvent under conditions to produce a compound having the structure:

##STR00003##

and (b) maintaining the compound produced in step (a) in a second suitable solvent under conditions sufficient to produce the trifluoromethoxylated aryl or trifluormethoxylated heteroaryl having the structure:

##STR00004##

The invention provides amides that inhibit cellular necrosis and/or human receptor interacting protein 1 kinase (RIP1), including corresponding sulfonamides, and pharmaceutically acceptable salts, hydrides and stereoisomers thereof. The compounds are employed in pharmaceutical compositions, and methods of making and use, including treating a person in need thereof with an effective amount of the compound or composition, and detecting a resultant improvement in the person's health or condition.

The disclosure provides a capture system and methods for isolating cysteine-containing peptides from biological fluid and proteolytic mixtures. The disclosure also provides compounds of formulae (II), (III), and (IV), useful in methods of the invention. ##STR00001##

The disclosure provides a capture system and methods for isolating cysteine-containing peptides from biological fluid and proteolytic mixtures. The disclosure also provides compounds of formulae (II), (III), and (IV), useful in methods of the invention. ##STR00001##

The present invention provides a novel method for treating cancer that comprises administering a compound represented by formula (I) and/or a chemotherapeutic agent to a subject. The present invention further provides a novel kit that comprises a compound represented by formula (I) and a chemotherapeutic agent for treating cancer.

The present invention provides a novel method for treating cancer that comprises administering a compound represented by formula (I) and/or a chemotherapeutic agent to a subject. The present invention further provides a novel kit that comprises a compound represented by formula (I) and a chemotherapeutic agent for treating cancer.

The present invention relates to dipeptidyl ketoamide m-methoxyphenyl derivatives and their use in the treatment of diseases and conditions associated with elevated calpain activity, such as heart injury caused by infarction, ischemia with or without reperfusion, neurodegenerative disorders, malaria, diabetic nephropathy, neurotoxicity induced by HIV virus, cancer, and fibrotic diseases.

The present invention relates to dipeptidyl ketoamide m-methoxyphenyl derivatives and their use in the treatment of diseases and conditions associated with elevated calpain activity, such as heart injury caused by infarction, ischemia with or without reperfusion, neurodegenerative disorders, malaria, diabetic nephropathy, neurotoxicity induced by HIV virus, cancer, and fibrotic diseases.