Discovery, Development, and SAR of Aminothiazoles as LIMK Inhibitors with Cellular Anti-Invasive Properties.

Autor:	Charles MD; Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K., Brookfield JL; Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K., Ekwuru TC; Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K., Stockley M; Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K., Dunn J; Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K., Riddick M; Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K., Hammonds T; Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K., Trivier E; Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K., Greenland G; Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K., Wong AC; Cancer Research Technology Discovery Laboratories, London Bioscience Innovation Centre , Royal College Street, London NW1 0NH, U.K., Cheasty A; Cancer Research Technology Discovery Laboratories , Jonas Webb Building, Babraham Research Campus, Cambridge CB22 3AT, U.K., Boyd S; CompChem Solutions Ltd, St John's Innovation Centre , Cambridge CB4 0WS, U.K., Crighton D; Beatson Institute, Cancer Research U.K. , Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K., Olson MF; Beatson Institute, Cancer Research U.K. , Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K.
Jazyk:	angličtina
Zdroj:	Journal of medicinal chemistry [J Med Chem] 2015 Oct 22; Vol. 58 (20), pp. 8309-13. Date of Electronic Publication: 2015 Sep 30.
DOI:	10.1021/acs.jmedchem.5b01242
Abstrakt:	As part of a program to develop a small molecule inhibitor of LIMK, a series of aminothiazole inhibitors were discovered by high throughput screening. Scaffold hopping and subsequent SAR directed development led to a series of low nanomolar inhibitors of LIMK1 and LIMK2 that also inhibited the direct biomarker p-cofilin in cells and inhibited the invasion of MDA MB-231-luc cells in a matrigel inverse invasion assay.
Databáze:	MEDLINE
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