The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.

The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II): ##STR00001## including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.5, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Compounds are provided that are useful as immunomodulators. The compounds have the following Formula (II): ##STR00001## including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.3, R.sup.4, R.sup.5, R.sup.6a, R.sup.6b, m and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Industrially viable and advantageous processes for the preparation of Ozanimod are described. The invention also discloses the intermediates obtained in the process.

##STR00001##

Provided is a process for preparing a compound of Formula A (Formula A) or a salt or solvate thereof, the process comprising the step of: a) Reacting the compound 1 (1) with a trialkyl orthoformate to provide a compound of Formula A or a salt or solvate thereof, wherein R is the alkyl moiety of the trialkyl orthoformate. Further provided is the compound 2 or a salt or solvate thereof. (2) The use of these compounds in the synthesis of 3-[5-Amino-4-(3-Cyanobenzoyl)-Pyrazol-1-yl]-N-Cyclopropyl-4-Methylbenzamide is also provided.

##STR00001##

Provided is a process for preparing a compound of Formula A (Formula A) or a salt or solvate thereof, the process comprising the step of: a) Reacting the compound 1 (1) with a trialkyl orthoformate to provide a compound of Formula A or a salt or solvate thereof, wherein R is the alkyl moiety of the trialkyl orthoformate. Further provided is the compound 2 or a salt or solvate thereof. (2) The use of these compounds in the synthesis of 3-[5-Amino-4-(3-Cyanobenzoyl)-Pyrazol-1-yl]-N-Cyclopropyl-4-Methylbenzamide is also provided.

##STR00001##

The present invention includes methods/processes and intermediates for preparing compounds having structural Formula (I): ##STR00001##
wherein X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

The present invention includes methods/processes and intermediates for preparing compounds having structural Formula (I): ##STR00001##
wherein X is alkyl, substituted alkyl, alkenyl, substituted alkenyl, heteroalkyl, substituted heteroalkyl, heteroalkenyl, or substituted heteroalkenyl.

The present disclosure relates to HIF-2α inhibitors and methods of making and using them for treating cancer. Certain compounds were potent in HIF-2α scintillation proximity assay, luciferase assay, and VEGF ELISA assay, and led to tumor size reduction and regression in 786-O xenograft bearing mice in vivo.