Sulfonylated aminothiazoles as new small molecule inhibitors of protein phosphatases

Based on a previously identified lead structure, SC-alpha alpha delta9, we have developed a versatile new chemical scaffold that can be readily modifi ed to generate libraries of both Tyr and dual specificity phosphatase inhib itors with reduced molecular weight and lipophilicity. The most potent anal ogue identified to dare, aminothiazole 8z, inhibits the dual specificity ph osphatase Cdc25B with a K-i of 4.6 +/- 0.4 muM and a Hill coefficient of 2. (C) 2001 Elsevier Science Ltd. Ail rights reserved.