1,2,4-triazolylaminoaryl (heteroaryl) sulfonamide derivatives

A method for treating a malignant melanoma, colon carcinoma, or adenocarcinoma in a subject in need thereof comprising administering to the subject an effective amount a compound of formula I

• wherein:
• X1 and X2 are independently selected from CH and N;
• R1 is selected from the group consisting of a carbocyclic, a heteroaryl, and a heterocyclic, and wherein R1 is optionally substituted with one or more substitutents independently selected from the group consisting of amido, phosphonato, phosphine, carboxyl, thiocarbonyl, sulfonyl, nitro, thiol, thioether, amine, cyano, N—(C1-6-alkyl)amino, N,N—(C1-6-alkyl)2-amino, sulfonamide, ketone, aldehyde, ester, halogen, oxygen, haloalkyl, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, hydroxyl and C1-6-alkoxyl;
• R2 is selected from the group consisting of hydrogen, hydroxy, nitro, amino, carboxy, carbamoyl, halo, cyano, trifluoromethyl, trifluoromethoxy, sulphamoyl, mercapto, C1-6-alkyl, C2-6-alkenyl, C2-6-alkynyl, C1-6-alkoxyl, N—(C1-6-alkyl)amino, N,N—(C1-6-alkyl)2-amino, and sulfonyl;
• R3 and R4 are independently selected from the group consisting of hydrogen, —CH2OPO3R5R6, —CH2OCOR7, —CH2OCO2R7, —CH2OCONHR7, —COR7, wherein R3 and R4 are not simultaneously hydrogen;
• R3′ is selected from the group consisting of hydrogen, heterocyclic and C1-8alkyl, wherein C1-8alkyl is optionally substituted with one or more of —CO2H, —CO2(C1-6)alkyl, hydroxy, C1-6alkoxy, amino, aminoacylamino, N—(C1-6-alkyl)amino, N,N—(C1-6alkyl)2-amino, heterocyclic or heteroaryl;
• R5 and R6 are each selected from the group consisting of hydrogen, C1-6alkyl, Na, K and NH4 and are the same unless either R5 or R6 is absent, hydrogen or C1-6alkyl, in which case the other is different, or alternatively, R5 and R6 together represent calcium or magnesium;
• R7 is heterocyclic or C1-6alkyl, wherein C1-6alkyl is optionally substituted with one or, more of —CO2H, —CO2(C1-6)alkyl, amino, amino-COR8, carbamoyl, carbamoyl(C1-6)alkyl, guanidino, mercapto, thio(C1-6)alkyl, hydroxy, N—(C1-6-alkyl)amino, N,N—(C1-6-alkyl)2-amino, aryl optionally substituted on aryl with one or more of C1-4-alkyl, C1-4-alkoxy, hydroxy, halogen, amino, aminoalkyl, nitro or cyano, heterocyclic, —(OCH2CH2)nOCH3 where n is 0-400, —(OCH2CH2)nOH where n is 0-400, or —(OCH2CH2)nOCH2CO2H where n is 0-400;
• and
• R8 is C1-6alkyl optionally substituted with one or more of —CO2H, —CO2(C1-6)alkyl, amino, aminoacylamino, carbamoyl, carbamoyl(C1-6)alkyl, guanidino, mercapto, thio(C1-6)alkyl, hydroxy, N—(C1-6-alkyl)amino, N,N—(C1-6-alkyl)2-amino, aryl optionally substituted on aryl with one or more of C1-4-alkyl, C1-4-alkoxy, hydroxy, halogen, amino, aminoalkyl, nitro or cyano, heterocyclic, —(OCH2CH2)nOCH3 where n is 0-400, —(OCH2CH2)nOH where n is 0-400, or —(OCH2CH2)nOCH2CO2H where n is 0-400;
• or a pharmaceutically acceptable salt thereof.