Provided herein are compounds useful for binding to one or more histone deacetylase enzymes (HDACs). The present application further provides radiolabeled compounds useful as a radiotracer for position emission tomography imaging of HDAC. Methods for prepared unlabeled and labeled compounds, diagnostic methods, and methods of treating diseases associated HDAC are also provided.

Provided herein are compounds useful for binding to one or more histone deacetylase enzymes (HDACs). The present application further provides radiolabeled compounds useful as a radiotracer for position emission tomography imaging of HDAC. Methods for prepared unlabeled and labeled compounds, diagnostic methods, and methods of treating diseases associated HDAC are also provided.

The present invention provides a process of producing a trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without substitution; and
R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.2, —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 trifluoromcthoxylated aryl or trifluoromothoxylated heteroaryl having the structure: ##STR00001##
wherein
A is an aryl or heteroaryl, each with or without substitution; and
R.sub.1 is —H, -(alkyl), -(alkenyl), -(alkynyl), -(aryl), -(heteroaryl), -(alkylaryl), -(alkylheteroaryl), —NH-(alkyl), —N(alkyl).sub.2, —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##

Inhibitors of mTOR, MEK, JAK and PI3K and compositions containing the same are disclosed. Methods of using the inhibitors in the treatment of a variety of diseases and conditions wherein inhibition of one or more of mTOR, MEK, JAK and PI3K provides a benefit also are disclosed. Methods of using chemical attachment moieties and linkers for the purposes of modifying compound solubility and/or lymphatic absorption are also disclosed.

Inhibitors of mTOR, MEK, JAK and PI3K and compositions containing the same are disclosed. Methods of using the inhibitors in the treatment of a variety of diseases and conditions wherein inhibition of one or more of mTOR, MEK, JAK and PI3K provides a benefit also are disclosed. Methods of using chemical attachment moieties and linkers for the purposes of modifying compound solubility and/or lymphatic absorption are also disclosed.

A surface treatment agent used for treating a substrate which has a surface having two or more regions made of materials that are different from each other, the agent including a compound (H) represented by Formula (H-1). In the formula, R.sup.1 represents a linear or branched alkyl group having 1 to 30 carbon atoms, a linear or branched fluorinated alkyl group having 1 to 30 carbon atoms, an aromatic hydrocarbon group, or a cycloalkyl group having 3 to 12 carbon atoms, and R.sup.2 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, or a cycloalkyl group having 3 to 12 carbon atoms)

##STR00001##

A surface treatment agent used for treating a substrate which has a surface having two or more regions made of materials that are different from each other, the agent including a compound (H) represented by Formula (H-1). In the formula, R.sup.1 represents a linear or branched alkyl group having 1 to 30 carbon atoms, a linear or branched fluorinated alkyl group having 1 to 30 carbon atoms, an aromatic hydrocarbon group, or a cycloalkyl group having 3 to 12 carbon atoms, and R.sup.2 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, or a cycloalkyl group having 3 to 12 carbon atoms)

##STR00001##

This disclosure relates generally to cannabinoid derivatives having the structural formula (I), pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives. In some embodiments, R.sup.1 is —CH.sub.2CH═C(CH.sub.3).sub.2, R.sup.2 is methyl, R.sup.3 is CsHn, R.sup.4 is —C(O)N(R.sup.4a)(R.sup.4b), R.sup.5 is H, R.sup.6 is OH, and R.sup.7 is H. Compounds of the present disclosure were tested in agonist and antagonist mode for both the CB1 and CB2 receptors. The tested compounds were generally found to exhibit activity in antagonist mode at the CB1 and CB2 receptor.

This disclosure relates generally to cannabinoid derivatives having the structural formula (I), pharmaceutical compositions comprising them, and methods of using the cannabinoid derivatives. In some embodiments, R.sup.1 is —CH.sub.2CH═C(CH.sub.3).sub.2, R.sup.2 is methyl, R.sup.3 is CsHn, R.sup.4 is —C(O)N(R.sup.4a)(R.sup.4b), R.sup.5 is H, R.sup.6 is OH, and R.sup.7 is H. Compounds of the present disclosure were tested in agonist and antagonist mode for both the CB1 and CB2 receptors. The tested compounds were generally found to exhibit activity in antagonist mode at the CB1 and CB2 receptor.