Arylsulfonamide derivatives as C-Jun-N-Terminal Kinases (JNK's) inhibitors

A sulfonamide according to formula I

• a geometrical isomer thereof, an optically active form thereof, an enantiomer thereof, a diastereomer thereof, a mixture thereof, or a salt thereof
• wherein:
• Ar1 is a substituted or unsubstituted aryl group;
• X is O or S;
• Ar2 is a substituted or unsubstituted thienylene group;
• R1 and R2 are independently selected from the group consisting of hydrogen and a C1-C6-alkyl group;
• Ra, Ra′, Rb, Rb′ are independently selected from the group consisting of hydrogen and C1-C6-alkyl;
• or Ra′ and Ra or Rb′ together with the carbon atoms they are linked, form a substituted or unsubstituted 5-8-membered saturated, partially unsaturated or aromatic ring containing optionally one or more heteroatoms selected from O, N, S;
• R3 is selected from the group consisting of H, C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, aryl, heteroaryl, 3-8 membered cycloalkyl optionally containing 1-3 heteroatoms selected from the group consisting of N, O, and S;
• aryl C1-C10-alkyl and heteroaryl C1-C10-alkyl;
• or R3 and Ra or Ra′ form, together with the N atom linked to R3, a 5-8-membered saturated ring, containing optionally at least one further heteroatom selected from O, N, S;
• R4 is selected from the group consisting of H and —C(H)R5R6;
• R5 and R6 are independently selected from the group consisting of H, C1-C10-alkyl, C2-C10-alkenyl, C2-C10-alkynyl, aryl, heteroaryl, 3-8 membered cycloalkyl optionally containing 1-3 heteroatoms selected from the group consisting of N, O, and S;
• aryl C1-C10-alkyl and heteroaryl C1-C10-alkyl;
• m is an integer from 1 to 5;
• n is an integer from 0 to 2;
• and
• p is an integer from 1 to 10;
• wherein the compound according to formula I is
• selected from the group consisting of
• 4-Chloro-N-{5-[1-(4-trifluoromethyl-benzyl)-piperidin-3-ylsulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-{5-[2,2-dimethyl-3-(4-trifluoromethyl-benzylamino)-propylsulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-(5-{3-[methyl-(4-trifluoromethyl-benzyl)-amino]-propylsulfamoyl}-thiophen-2-ylmethyl)-benzamide;
• 4-Chloro-N-{5-[3-(hexyl-methyl-amino)-propylsulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-{5-[2-(4-trifluoromethyl-benzylamino)-cyclohexylsulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-[5-(2 hexylamino-ethylsulfamoyl)-thiophen-2-ylmethyl]-benzamide;
• 4-Chloro-N-{5-[1-(4-trifluoromethyl-benzyl)-piperidin-4-ylsulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-[5-(3-hexylamino-2,2-dimethyl-propylsulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-{5-[3-(4-trifluoromethyl-benzylamino)-benzylsulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-{5-[3-(4-trifluoromethyl-benzylamino)-propylsulfamoyl]thiophen-2-ylmethyl)benzamide;
• 4-Chloro-N (5-{[1-(4-trifluoromethyl-benzyl)-piperidin 3-ylmethyl]-sulfamoyl}-thiophen-2-ylmethyl)-benzamide;
• 4-Chloro-N (5-{methyl-[3-(4-trifluoromethyl-benzylamino)-propyl]-sulfamoyl}-thiophen-2-ylmethyl)-benzamide;
• 4-Chloro-N-{5-[(3-hexylamino-propyl)-methyl sulfamoyl]-thiophen-2-ylmethyl}-benzamide;
• 4-Chloro-N-(5-{[1-(4-trifluoromethyl-benzyl)-pyrrolidin-2-ylmethyl]-sulfamoyl}-thiophen-2-ylmethyl)-benzamide;
• and
• 4-Chloro-N-{5-[2,2-dimethyl-3-(3-trifluoromethanesulfonyl-phenylamino]-propylsulfamoyl]-thiophen-2-ylmethyl}-benzamide.