1,8-dihydroxyanthraquinone-6-carboxamide derivatives as inhibitors of T-cell proliferation for treatment of autoimmune or inflammatory conditions

摘要

A compound of general formula (B1/B): EMI ID=1.1 HE=41 WI=77 LX=908 LY=81 TI=CF PCwherein: ```R1 and R2 are the same or different and are each H, C1-4 alkyl or COR5; ```R3 is H or C1-4 alkyl; and ```R4 is C1-4 alkyl substituted with R6, C2-4 alkyl substituted with R7, aryl substituted with R7 or heteroaryl optionally substituted with R7, C3-6cycloalkyl optionally substituted with R7 or C4-6 heterocycloalkyl optionally substituted with R7; or ```NR3R4 is a four to seven-membered ring which is optionally substituted with R7 and can contain one or more additional heteroatoms taken from O, S(O)n and NR1 wherein n is 0-2; ```R5 is C1-4 alkyl, aryl or heteroaryl; ```R6 is aryl substituted with R7, heteroaryl optionally substituted with R7, C3-6cycloalkyl optionally substituted with R7 or C4-6 heterocycloalkyl optionally substituted with R7; ```R7 is OR3, CO2R3, N(R3)2 where each R3 is the same or different or form a four to seven-membered ring which may contain one or more additional heteroatoms taken from O, S(O)n and NR1 wherein n is 0-2, or N(R3)2 is a five or six-membered ring such as a lactam, succinimide or hydantoin of the formula: EMI ID=1.2 HE=36 WI=89 LX=921 LY=1717 TI=CF PC```or a salt, solvate or hydrate thereof, may have utility in the treatment of an autoimmune or inflammatory condition. Such conditions include a chronic degenerative disease (such as rheumatoid arthritis, osteoarthritis or osteoporosis), a chronic demyelinating disease (such as multiple sclerosis), a respiratory disease (such as asthma or allergic rhinitis or chronic obstructive pulmonary disease [COPD]), an inflammatory bowel disease [IBD](such as ulcerative colitis or Chron's disease), a dermatological condition (such as psoriasis, scleroderma or atopic dermatitis) a dental disease (such as periodontal disease or gingivitis), diabetic nephropathy, lupus nephritis, IgA nephropathy, glomerulonephritis, systemic lupus erythematosus (SLE) or graft vs host disease. These carboxamide derivatives are capable of inhibiting T-cell proliferation in assays. In addition, the physiochemical properties of the template can be greatly enhanced by utilising the amide substituent to introduce solubility-enhancing groups.