M. A. Novikov, K. V. Potapov, R. A. Novikov, P. N. Solyev, Yu. V. Tomilov, S. N. Kochetkov, A. A. Makarov, V. A. Mitkevich, “A convenient synthesis of a chlorobenzothiophenyl-indole-based inhibitor of bacterial cystathionine γ-lyase”, Mendeleev Commun., 2024, Volume 34, Issue 2,Pages <nobr>255

This article is cited in 2 papers

Communications

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

M. A. Novikov^ab, K. V. Potapov^ab, R. A. Novikov^abc, P. N. Solyev^a, Yu. V. Tomilov^b, S. N. Kochetkov^a, A. A. Makarov^a, V. A. Mitkevich^ad

^a V.A. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation
^b N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russian Federation
^c Sirius University of Science and Technology, Sochi, Russian Federation
^d Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation

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).

Keywords: antibacterial compounds, indole-based inhibitors, NL3, bCSE, antibiotics potentiation, benzo[b]thiophenes, indoles, cross-coupling.

Language: English

DOI: 10.1016/j.mencom.2024.02.030

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