De Novo Synthesis of a Potent
LIMK1 Inhibitor

Brad E. Sleebs; Ian P. Street; Xian Bu; Jonathan B. Baell

doi:10.1055/s-0029-1219230

PAPER

De Novo Synthesis of a Potent LIMK1 Inhibitor

Brad E. Sleebs*^a,b, Ian P. Street^a,b, Xian Bu^c, Jonathan B. Baell^a,b
^a The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia
^b Cancer Therapeutics-CRC P/L, 4 Research Ave, La Trobe R&D Park, Bundoora, Victoria 3086, Australia
Fax: +61(3)93452129; e-Mail: sleebs@wehi.edu.au;
^c SYNthesis Med Chem P/L, 528 Ruiqing Road, Heqing, Zhangjiang Modern Medical Device Park, Shanghai 201203, P. R. of China

Abstract

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Abstract

A potent LIMK1 inhibitor, BMS4, was synthesised in six steps starting from pyrazine-2-carboximidamide, offering a significant improvement over current methods available in the literature.

Key words

kinase inhibitor - nitrogen heterocycles - pyrimidine - Suzuki coupling - cyclization

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Referenzen

References

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Bristol-Myers Squibb did not assign compound 1 a BMS compound number. However in the Bristol-Myers Squibb publication,^³ compound 1 was referred to as ‘compound 4’. Hence, for identification purposes, we named compound 1 ‘BMS4’.

Communication with SYNthesis Med Chem.

The authors noted that the quality of Pd(PPh₃)₄ dramatically influences the reaction outcome.

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Experimental details and conditions for the LIMK1 Transcreener Fluorescence Polarisation assay are available from the authors on request.