The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

The present invention provides pharmaceutically active pyrrolo[2,3-d]pyrimidinyl and pyrrolo[2,3-d]pyridinyl acrylamides and analogues thereof. Such compounds are useful for inhibiting Janus Kinase (JAK). This invention also is directed to compositions comprising methods for making such compounds, and methods for treating and preventing conditions mediated by JAK.

Mitochondrial targeting compounds for the treatment of cancer and other disorders associated with mitochondrial function, including diabetes, autoimmune diseases, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases and their preparation. The present invention is also directed to the pharmaceutical compositions and treatment methods, prodrugs based on those compounds and the use thereof.

Mitochondrial targeting compounds for the treatment of cancer and other disorders associated with mitochondrial function, including diabetes, autoimmune diseases, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases and their preparation. The present invention is also directed to the pharmaceutical compositions and treatment methods, prodrugs based on those compounds and the use thereof.

Described herein are compounds that are inhibitors of autophagy and their use in the treatment of disorders such as cancers.

Described herein are compounds that are inhibitors of autophagy and their use in the treatment of disorders such as cancers.

The present invention relates to MEK inhibitors that are capable of displaying one or more beneficial therapeutic effects. The MEK inhibitors can be used in the prevention and/or treatment of hantavirus infection.

The present invention relates to MEK inhibitors that are capable of displaying one or more beneficial therapeutic effects. The MEK inhibitors can be used in the prevention and/or treatment of hantavirus infection.

A method of administering to a patient in need thereof or contacting with a biological sample, a compound related to Formula I-e ##STR00001##
or pharmaceutically acceptable compositions thereof, is useful to inhibit activity of TLR7/8 or a mutant thereof and/or to treat a TLR7/8-mediated disorder.

The discovery of mutant or fusion kinases that drive oncogenesis, and the subsequent approval of specific inhibitors for these enzymes, has been instrumental in the management of some cancers. However, acquired resistance remains a significant problem in the clinic, limiting the long-term effectiveness of most of these drugs. Herein is demonstrated a strategy to overcome this resistance through drug-induced MEK cleavage (via direct procaspase-3 activation) combined with targeted kinase inhibition. This combination effect is shown to be general across diverse tumor histologies (melanoma, lung cancer, and leukemia) and driver mutations (mutant BRAF or EGFR, fusion kinases EML4-ALK and BCR-ABL). Caspase-3-mediated degradation of MEK kinases results in sustained pathway inhibition and substantially delayed or eliminated resistance in cancer cells in a manner superior to combinations with MEK inhibitors. These data suggest the generality of drug-mediated MEK kinase cleavage as a therapeutic strategy to prevent resistance to targeted anticancer therapies.