The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI/SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and/or polybromo-1 (PB-1) protein via ubiqitination and/or degradation by compounds. The compounds are useful in treatment of cancer.

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI/SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and/or polybromo-1 (PB-1) protein via ubiqitination and/or degradation by compounds. The compounds are useful in treatment of cancer.

The present invention addresses the problem of providing a pharmaceutical composition, in particular a compound suitable for prevention and/or treatment of an inflammatory disease and/or a neurodegenerative disease. The inventors of the present invention conducted extensive studies to find a compound that has suppressive action on NLRP3 inflammasome activation, and found that a substituted pyridazine compound has suppressive action on NLRP3 inflammasome activation, leading to completion of the present invention. The substituted pyridazine compound according to the present invention is expected to serve as a drug for prevention and/or treatment of an inflammatory disease and/or a neurodegenerative disease.

The invention relates to an improved process for synthesizing 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide of the formula: ##STR00001## Compound I is currently in clinical trials for the treatment of auto-immune and auto-inflammatory diseases such as psoriasis.

The invention relates to an improved process for synthesizing 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide of the formula: ##STR00001## Compound I is currently in clinical trials for the treatment of auto-immune and auto-inflammatory diseases such as psoriasis.

Compounds of the form in which Q is selected from —COOH—CH═NR.sup.12, —W, —CH.sub.2NHR.sup.13, —CH=0 and —CH(OR.sup.17).sub.2 capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer and formulations and methods of use of such compounds.

##STR00001##

Compounds of the form in which Q is selected from —COOH—CH═NR.sup.12, —W, —CH.sub.2NHR.sup.13, —CH=0 and —CH(OR.sup.17).sub.2 capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer and formulations and methods of use of such compounds.

##STR00001##

The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

##STR00001##

The present disclosure provides carboxamides and sulfonamides having Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, Y, B, X, and Z are defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of SMYD proteins such as SMYD3 or SMYD2. Compounds of the present disclosure are especially useful for treating cancer.

##STR00001##

The present invention provides an adaptive control system to control a plant using direct output feedback in which a function of the full plant state, as opposed to estimates thereof, is used for feedback control of the plant. The adaptive control system of this invention is therefore highly useful in the control of plants, particularly plants for controlling the physical properties of rolls of web material and more particularly a calendering apparatus. Accordingly, in a particularly preferred embodiment the adaptive control system of this invention controls loading of a calender apparatus, such as a pair of opposed rolls forming a calendering stack, based upon the physical properties of a previously processed web.