The inventors have used a differential nuclear staining (DNS) assay to discover compounds with cytotoxic activity against the CEM cell line that has been determined to be highly sensitive to a variety of anti-cancer compounds. Compounds were synthesized based on a pyrazole backbone structure. Several newly synthesized compounds have been tested to identify the compounds with highest activity. One compound identified is the SSK-3 compound which has been tested on cancer cell lines and determined that it induced apoptosis via phosphatidylserine membrane exposure and activation of caspase 3 in the CEM lymphoma cell line.

The inventors have used a differential nuclear staining (DNS) assay to discover compounds with cytotoxic activity against the CEM cell line that has been determined to be highly sensitive to a variety of anti-cancer compounds. Compounds were synthesized based on a pyrazole backbone structure. Several newly synthesized compounds have been tested to identify the compounds with highest activity. One compound identified is the SSK-3 compound which has been tested on cancer cell lines and determined that it induced apoptosis via phosphatidylserine membrane exposure and activation of caspase 3 in the CEM lymphoma cell line.

The present invention relates to an agent for protection of vascular endothelial cells, an agent for protection of blood brain spinal cord barrier, and an agent for protection of central nervous system, containing at least one compound selected from the group consisting of muvritinib, brexpiprazole, papaverine, bismuth-containing compounds, and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition for the treatment of diseases associated with blood brain spinal cord barrier disruption, containing at least one compound selected from the group consisting of muvritinib, brexpiprazole, papaverine, bismuth-containing compounds, and pharmaceutically acceptable salts thereof.

The present invention relates to an agent for protection of vascular endothelial cells, an agent for protection of blood brain spinal cord barrier, and an agent for protection of central nervous system, containing at least one compound selected from the group consisting of muvritinib, brexpiprazole, papaverine, bismuth-containing compounds, and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition for the treatment of diseases associated with blood brain spinal cord barrier disruption, containing at least one compound selected from the group consisting of muvritinib, brexpiprazole, papaverine, bismuth-containing compounds, and pharmaceutically acceptable salts thereof.

This invention is directed to selective androgen receptor degrader (SARD) compounds including heterocyclic rings and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

This invention is directed to selective androgen receptor degrader (SARD) compounds including heterocyclic rings and pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, triple negative breast cancer, other cancers expressing the androgen receptor, androgenic alopecia or other hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), abdominal aortic aneurysm (AAA), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.

Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

Methods and compositions for treating a subject hosting a non-ACTH-secreting pancreatic tumor are disclosed. The methods include administering to the subject a chemotherapeutic agent and a glucocorticoid receptor modulator (GRM), preferably a selective glucocorticoid receptor modulator (SGRM), to reduce the tumor load in the subject. The GRM may be a nonsteroidal GRM, and may be a nonsteroidal SGRM. The non-ACTH-secreting pancreatic tumor may be an exocrine pancreatic tumor. The nonsteroidal SGRM may be a nonsteroidal compound comprising: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure. Pharmaceutical compositions comprising a chemotherapeutic agent and a GRM are disclosed. The GRM in such pharmaceutical compositions may be a nonsteroidal GRM, and may be a SGRM, such as a nonsteroidal SGRM. The nonsteroidal SGRM may comprise: a fused azadecalin structure; a heteroaryl ketone fused azadecalin structure; or an octahydro fused azadecalin structure.

The present invention relates to indane compounds, methods of making them, pharmaceutical compositions containing them and their use as NRF2 activators. In particular, the invention relates to compounds of Formula (I) or Formula (II), and pharmaceutically acceptable salts thereof: ##STR00001##

The invention relates to daridorexant: Formula (I) or drochloric acid salt; for use in a method of treatment of sleep disorders such as especially insomnias, wherein daridorexant improves daytime performance, especially reduces daytime sleepiness associated to such sleep disorder

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