The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism.

Provided herein are methods for treating, preventing or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract, for example, those involving the esophagus. Also provided herein are pharmaceutical compositions useful for the methods of the present invention.

The present invention provides a compound of formula (I) or a salt thereof:

##STR00001##

wherein X, L, V, R.sub.1, R.sub.2, R.sub.3 and R.sub.4, are as defined herein.

The present invention provides a compound of formula (I) or a salt thereof:

##STR00001##

wherein X, L, V, R.sub.1, R.sub.2, R.sub.3 and R.sub.4, are as defined herein.

Provided are compositions and methods for treating or preventing nausea and vomiting in patients undergoing chemotherapy, radiotherapy, or surgery.

Provided herein are methods for treating, preventing or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract, for example, those involving the esophagus. Also provided herein are pharmaceutical compositions useful for the methods of the present invention.

The present invention relates to the delivery of oligomers for treating patients with a 5′ mutation in their DMD gene other than a DMD exon 2 duplication. The invention provides methods and materials for activating an internal ribosome entry site in exon 5 of the DMD gene resulting in translation of a functional truncated isoform of dystrophin. The methods and materials can be used for the treatment of muscular dystrophies arising from 5′ mutations in the DMD gene such as Duchenne Muscular Dystrophy or Becker Muscular Dystrophy.

The present invention provides a compound of formula (I) or a salt thereof: (I) wherein X, L, V, R.sub.1, R.sub.2, R.sub.3 and R.sub.4, are as defined herein. These compounds are inhibitors of 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2) and are used to treat hyperkalemia. ##STR00001##

The present invention provides a compound of formula (I) or a salt thereof: (I) wherein X, L, V, R.sub.1, R.sub.2, R.sub.3 and R.sub.4, are as defined herein. These compounds are inhibitors of 11-hydroxysteroid dehydrogenase type 2 (11-HSD-2) and are used to treat hyperkalemia. ##STR00001##

Methods and compositions are disclosed for diagnosing a patient suspected of suffering from, and for treating a patient suffering from, a disorder such as hypercortisolemia, metabolic syndrome, pre-diabetes, diabetes, Cushing's syndrome, Cushing's Disease, hyperglycemia secondary to hypercortisolemia, a liver disease, a cardiac disorder, high blood pressure, a blood clotting disorder, a cancer, a psychological disorder, weight gain, a disorder of glucose control, a bone disorder (e.g., osteoporosis), hypogonadism, pseudoacromegaly, pituitary tumors, functional hypercortisolism, ACTH secreting tumors, peripheral neuropathy, dyslipidemia and other disorders.

The methods and compositions include administration of a heteroaryl-ketone fused azadecalin glucocorticoid receptor modulator (GRM). The preferred heteroaryl-ketone fused azadecalin GRM is relacorilant ((R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone). In some cases, the GRM (e.g., relacorilant) is orally administered. In some cases, the GRM (e.g., relacorilant) is orally administered without food.