The present invention provides methods for inhibiting respiratory complex III in a cell. The present invention also provides methods for treating cancer in a subject.

The present invention provides methods for inhibiting respiratory complex III in a cell. The present invention also provides methods for treating cancer in a subject.

Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I:

##STR00001##

wherein R.sub.1 to R.sub.5 and X.sub.1 to X.sub.5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.

Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I:

##STR00001##

wherein R.sub.1 to R.sub.5 and X.sub.1 to X.sub.5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.

Methods of synthesis of hypervalent iodine reagents and methods for oxidation of organic compounds are disclosed.

Methods of synthesis of hypervalent iodine reagents and methods for oxidation of organic compounds are disclosed.

Disclosed is a method for preparing a compound of Formula 1 wherein Q and Z are as defined in the disclosure comprising distilling water from a mixture comprising a compound of Formula 2, a compound of Formula 3, a base comprising at least one compound selected from the group consisting of alkaline earth metal hydroxides of Formula 4 wherein M is Ca, Sr or Ba, alkali metal carbonates of Formula 4a wherein M.sup.1 is Li, Na or K, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene, and an aprotic solvent capable of forming a low-boiling azeotrope with water. Also disclosed is a method for preparing a compound of Formula 2 comprising (1) forming a reaction mixture comprising a Grignard reagent derived from contacting a compound of Formula 5 wherein X is Cl, Br or I with magnesium metal or an alkylmagnesium halide in the presence of an ethereal solvent, and then (2) contacting the reaction mixture with a compound of Formula 6 wherein Y is OR.sup.11 or NR.sup.12R.sup.13, and R.sup.11, R.sup.12 and R.sup.13 are as defined in the disclosure. Further disclosed is a method for preparing a compound of Formula 7 wherein Q and Z are as defined in the disclosure, using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the method disclosed above or using a compound of Formula 1 prepared by the method disclosed above. ##STR00001##

Disclosed is a method for preparing a compound of Formula 1 wherein Q and Z are as defined in the disclosure comprising distilling water from a mixture comprising a compound of Formula 2, a compound of Formula 3, a base comprising at least one compound selected from the group consisting of alkaline earth metal hydroxides of Formula 4 wherein M is Ca, Sr or Ba, alkali metal carbonates of Formula 4a wherein M.sup.1 is Li, Na or K, 1,5-diazabicyclo[4.3.0]non-5-ene and 1,8-diazabicyclo[5.4.0]undec-7-ene, and an aprotic solvent capable of forming a low-boiling azeotrope with water. Also disclosed is a method for preparing a compound of Formula 2 comprising (1) forming a reaction mixture comprising a Grignard reagent derived from contacting a compound of Formula 5 wherein X is Cl, Br or I with magnesium metal or an alkylmagnesium halide in the presence of an ethereal solvent, and then (2) contacting the reaction mixture with a compound of Formula 6 wherein Y is OR.sup.11 or NR.sup.12R.sup.13, and R.sup.11, R.sup.12 and R.sup.13 are as defined in the disclosure. Further disclosed is a method for preparing a compound of Formula 7 wherein Q and Z are as defined in the disclosure, using a compound of Formula 1 characterized by preparing the compound of Formula 1 by the method disclosed above or using a compound of Formula 1 prepared by the method disclosed above. ##STR00001##

Methods of treating presbyopia or cataract in a subject in need thereof are provided. The methods require administering to the subject an effective amount of a composition comprising a compound that inhibits the formation or dissolves high molecular weight aggregates of human ?-A-crystallin. Compositions containing certain compounds are believed to be also effective in the treatment of transthyretin (TTR)-associated amyloidosis, Prion, Creutzfeldt-Jakob, Gerstmann-Str?ussler-Scheinker disease and Ankyloblepharon-ectodermal dysplasia-cleft lip/palate syndrome.

Methods of treating presbyopia or cataract in a subject in need thereof are provided. The methods require administering to the subject an effective amount of a composition comprising a compound that inhibits the formation or dissolves high molecular weight aggregates of human ?-A-crystallin. Compositions containing certain compounds are believed to be also effective in the treatment of transthyretin (TTR)-associated amyloidosis, Prion, Creutzfeldt-Jakob, Gerstmann-Str?ussler-Scheinker disease and Ankyloblepharon-ectodermal dysplasia-cleft lip/palate syndrome.