Provided are compounds that act as covalent inhibitors of mitogen-activated protein kinase kinase 7 (MKK7 enzyme), method of preparation and uses thereof.

The present invention is directed to acylsulfonamide derivatives, pharmaceutical compositions containing them and their use as antagonists of the EP3 receptor, for the treatment of for example, impaired oral glucose tolerance, elevated fasting glucose, Type II Diabetes Mellitus, Syndrome X (also known as Metabolic Syndrome) and related disorders and complications thereof.

The present invention is directed to acylsulfonamide derivatives, pharmaceutical compositions containing them and their use as antagonists of the EP3 receptor, for the treatment of for example, impaired oral glucose tolerance, elevated fasting glucose, Type II Diabetes Mellitus, Syndrome X (also known as Metabolic Syndrome) and related disorders and complications thereof.

The invention provides novel compounds having the general formula I: ##STR00001##
wherein R.sup.1, R.sup.B1, R.sup.B2, n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

The invention provides novel compounds having the general formula I: ##STR00001##
wherein R.sup.1, R.sup.B1, R.sup.B2, n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of using the compounds.

The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

Disclosed herein are Notch transcriptional activation complex kinase (“NACK”) inhibitors, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein include compounds of Formula (la) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

##STR00001##

Disclosed herein are Notch transcriptional activation complex kinase (“NACK”) inhibitors, and methods for their use in treating or preventing diseases, such as cancer. The inhibitors described herein include compounds of Formula (la) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

##STR00001##

Compounds of formula (I) wherein, R.sup.1, R.sup.2, R.sup.3, R.sup.4a, R4b and R.sup.5 are described herein, or a stereoisomer, enantiomer or tautomer thereof or mixtures thereof, or a pharmaceutically acceptable salt or solvate thereof, are described herein, as well as other compounds. These compounds are useful in treating inflammation and/or pain. Compositions comprising a compound of the invention are also disclosed, as are methods of using the compounds to treat inflammation and/or pain.

##STR00001##