Arylsulfonamide ccr3 agtagonists

摘要

Disclosed are 4-(phenoxy)-3-(piperazin-1-ylsulfonyl)benzonitrile derivatives as represented by the general formula (I), wherein X is O or S; RYa is S(O)R1a, S(O)2R1a, S(O)NR1bR1c, or S(O)2NR1bR1c; and wherein the remaining substituents are as defined herein. Representative compounds include 4-(3,5-dimethylphenoxy)-3-(4-p-toluenesulphonylpiperazin-1-ylsulfonyl)benzonitrile, 3-(4-mesyl-piperazin-1-ylsulfonyl)-4-(3,5-dimethylphenoxy)benzonitrile, 4-(2,5-dichlorophenoxy)-3-(4-(dimethylaminosulphonyl)piperazin-1-ylsulfonyl)benzonitrile and 4-mesyl-1-([2-(2,5-dichloro-phenylthio)-5-nitro-phenyl]sulphonyl)-piperazine. Further disclosed is a pharmaceutical composition comprising a compound as defined above, or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, or tautomer thereof; one or more pharmaceutically acceptable carriers or excipients; and optionally a second therapeutic agent; for the treatment, prevention, or amelioration of one or more symptoms of a CCR3-mediated disorder, disease, or condition in a subject, such as asthma, allergic asthma, exercise induced asthma, allergic rhinitis, perennial allergic rhinitis, seasonal allergic rhinitis, atopic dermatitis, contact hypersensitivity, contact dermatitis, conjunctivitis, allergic conjunctivitis, eosinophilic bronchitis, food allergies, eosinophilic gastroenteritis, inflammatory bowel disease, ulcerative colitis, Crohn’s disease, mastocytosis, hyper IgE syndrome, systemic lupus erythematous, psoriasis, acne, multiple sclerosis, allograft rejection, reperfusion injury, chronic obstructive pulmonary disease, Churg-Strauss syndrome, sinusitis, basophilic leukemia, chronic urticaria, basophilic leukocytosis, psoriasis, eczema, COPD (chronic obstructive pulmonary disorder), arthritis, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, and cardiovascular disorders.