A convenient synthesis of a chlorobenzothiophenyl-indole-based inhibitor of bacterial cystathionine γ-lyase

Abstract

A convenient and efficient synthesis of 3-{[6-(7-chloro- benzo[b]thiophen-2-yl)-1H-indol-1-yl]methyl}-1H-pyrazole- 5-carboxylic acid (NL3), which is currently among the most active and promising bacterial cystathionine γ-lyase (bCSE) inhibitors, has been developed. It is based on shifting the key stage of [Pd]-catalyzed cross-coupling of the indole and benzothiophene counterparts to the beginning of the synthetic scheme, with the polarity reversal of the components being coupled, to give 6-(7-chlorobenzo[b]thiophen-2-yl)-1H- indole as the key intermediate. The STD NMR method was used to estimate the NL3 compound obtained in the optimized synthesis as a ligand to saCSE (the main producer of H2S in pathogenic S. aureus).