The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel and potent (7.1 mu M) inhibitor of Hsp90 ATPase activity. Here, we describe the synthesis of CCT018159 and a number of close analogues together with data on their biochemical properties. Some initial structure-activity relationships are discussed, as well as the crystal structure of CCT018159 bound to Hsp90. (c) 2005 Elsevier Ltd. All rights reserved.