| 摘要 |
Sulfonamide compounds (I) and their salts, diastereomers, racemates and meso-forms, are new. Sulfonamide compounds of formula (I) and their salts, diastereomers, racemates and meso-forms, are new. [Image] R 1aryl, aryl-lower alkyl, aryl-lower alkenyl, heteroaryl or heteroaryl-lower alkyl; R 2lower alkyl, CF 3, lower alkoxy-lower alkyl, lower alkenyl, lower alkynyl, aryl, aryl-lower alkyl, aryl-lower alkenyl, heterocyclyl, heterocyclyl-lower alkyl, heteroaryl, heteroaryl-lower alkyl, cycloalkyl or cycloalkyl-lower alkyl; R 3phenyl (optionally substituted by 1-3 lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, amino, lower alkylamino, amino-lower alkyl, CF 3, OCF 3, halo, lower alkylthio, OH, hydroxy-lower alkyl, CN, carboxyl, lower alkanoyl or formyl), benzofuranyl, aryl or heteroaryl; R 4H, halo, CF 3, lower alkyl, lower alkylamino, lower alkoxy, lower alkylsulfono, lower alkylsulfinyl, lower alkylthio, lower alkylthio-lower alkyl, hydroxy-lower alkyl, lower alkyl-oxy-lower alkyl, hydroxy-lower alkyl-oxy-lower alkyl, hydroxy-lower alkylamino, lower-alkylamino-lower alkyl, amino, di(lower alkyl)amino, [N-(hydroxy-lower alkyl)-N-(lower alkyl) amino], aryl, arylamino, aryl-lower alkylamino, arylthio, aryl-lower alkylthio, aryloxy, aryl-lower alkyloxy, aryl-lower alkyl, arylsulfinyl, heteroaryl, heteroaryloxy, heteroaryl-lower alkyloxy, heteroaryl-amino, heteroaryl-lower alkylamino, heteroarylthio, heteroaryl-lower alkylthio, heteroaryl-lower alkyl, heteroaryl-sulfinyl, heterocyclyl, heterocyclyloxy, heterocyclyl-lower alkyloxy, heterocyclyl-amino, heterocyclyl-lower alkylamino, heterocyclylthio, heterocyclyl-lower alkylthio, heterocyclyl-lower alkyl or heterocyclyl-sulfinyl; R 6H, lower alkyl, cycloalkyl, heterocyclyl, heteroaryl, aryl, cycloalkyl-lower alkyl, heterocyclyl-lower alkyl, heteroaryl-lower alkyl, aryl-lower alkyl, lower alkoxy-lower alkyl, lower alkylthio-lower alkyl, lower alkylamino-lower alkyl, lower alkenyl or lower alkynyl; n : 2-5; and X : O, S, NH, CH 2 or bond. An independent claim is also included for the preparation of (I). ACTIVITY : Antimigraine; hypotensive; cardiant; vasotropic; antianginal; cytostatic; antiasthmatic; antiinflammatory; nephrotropic; cerebroprotective; nootropic; hemostatic; antiarteriosclerotic; antiulcer; auditory; opthalmological; antibacterial; antisickling; antidiabetic; immunosuppressant. MECHANISM OF ACTION : Endothelin ET A and ET B antagonist. Competitive binding assays were carried out on CHO cells expressing human recombinant ET A or ET B receptors. p-t-butyl-N-[6-(3-(2-thiophenesulfonamido)propoxy)-5-(o-methoxyphenoxy)-2-(2-cyclopropyl)-4-pyrimidinyl]benzenesulfonamide (Id) gave IC 50's of 14.8 and 1.86 nM respectively for ET A and ET B inhibition. |
