4-Amino derivatives of the Hsp90 inhibitor CCT018159.

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Barril X, Beswick MC, Collier A, Drysdale MJ, Dymock BW, Fink A, Grant K, Howes R, Jordan AM, Massey A, Surgenor A, Wayne J, Workman P, Wright L

4-Amino derivatives of the Hsp90 inhibitor CCT018159.

Bioorg Med Chem Lett. 2006 May 1;16(9):2543-8. Epub 2006 Feb 9.

PubMed ID

16480864 [ View in PubMed

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Abstract

Novel piperazinyl, morpholino and piperidyl derivatives of the pyrazole-based Hsp90 inhibitor CCT018159 are described. Structure-activity relationships have been elucidated by X-ray co-crystal analysis of the new compounds bound to the N-terminal domain of human Hsp90. Key features of the binding mode are essentially identical to the recently reported potent analogue VER-49009. The most potent of the new compounds has a methylsulfonylbenzyl substituent appended to the piperazine nitrogen, possesses an IC50 of less than 600 nM binding against the enzyme and demonstrates low micromolar inhibition of tumour cell proliferation.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
4-CHLORO-6-(4-PIPERAZIN-1-YL-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOL	Heat shock protein HSP 90-alpha	IC 50 (nM)	2000	N/A	N/A	Details
4-CHLORO-6-(4-PIPERAZIN-1-YL-1H-PYRAZOL-5-YL)BENZENE-1,3-DIOL	Heat shock protein HSP 90-alpha	IC 50 (nM)	8200	N/A	N/A	Details