Sulfonylated pyrrole-2-indolinone derivatives as kinase inhibitors

Example 1

3-{4-(2-Dimethylcarbamoyl-ethyl)-2-methyl-5-[2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-1H-pyrrole-3-sulfonyl}-benzoic acid

Oxindole (Aldrich) was condensed with 3-[4-(2-dimethylcarbamoyl-ethyl)-5-formyl-2-methyl-1H-pyrrole-3-sulfonyl]-benzoic acid and piperidine in ethanol to give the titled compound.

Example 2

3-{4-(2-Dimethylcarbamoyl-ethyl)-5-[5-fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2-methyl-1H-pyrrole-3-sulfonyl}-benzoic acid

5-Fluorooxindole (Combi-block) was condensed with 3-[4-(2-dimethylcarbamoyl-ethyl)-5-formyl-2-methyl-1H-pyrrole-3-sulfonyl]-benzoic acid (prepared as described above in the synthesis of aldehyde 7) and piperidine in ethanol to give the titled compound.

1HNMR (400 MHz, DMSO-d6) δ 8.25 (s, 1H), 8.06 (d, 1H), 7.81 (d, 1H), 7.72 (m, 2H), 7.50 (m, 1H), 6.96 (m, 1H), 6.84 (m, 1H), 3.10 (m, 2H), 2.76 (s, 3H, CH3), 2.70 (s, 3H, CH3), 2.58 (s, 3H, CH3), 2.29 (m, 2H).

MS m / z 524 [M−1].

Example 3

3-[5-[5-Chloro-2-oxo-1,2-dihydrb-indol-(3Z)-ylidenemethyl]-4-(2-dimethylcarbamoyl-ethyl)-2-methyl-1H-pyrrole-3-sulfonyl]-benzoic acid

5-Chlorooxindole (Aldrich) was condensed with 3-[4-(2-dimethylcarbamoyl-ethyl)-5-formyl-2-methyl-1H-pyrrole-3-sulfonyl]-benzoic acid (prepared as described above in the synthesis of aldehyde 7) and piperidine in ethanol to give the titled compound.