De Novo Synthesis of a Potent LIMK1 Inhibitor

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

References

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4

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’.

5

Communication with SYNthesis Med Chem.

6

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

8

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