Details

Autor(en) / Beteiligte

• Patnaik, Anup
• Axford, Laura
• Deng, Lin
• Cohick, Evan
• Ren, Xianglin
• Loi, Sally
• Kecman, Sam
• Hollis-Symynkywicz, Micah
• Harrison, Tyler J.
• Papillon, Julien P.N.
• Dales, Natalie
• Hamann, Lawrence G.
• Lee, Lac
• Regard, Jean B.
• Marcinkeviciene, Jovita
• Marro, Martin L.
• Patterson, Andrew W.

Titel

Discovery of a novel indole pharmacophore for the irreversible inhibition of myeloperoxidase (MPO)

Ist Teil von

• Bioorganic & medicinal chemistry, 2020-06, Vol.28 (12), p.115548-115548, Article 115548

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2020

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• [Display omitted] Myeloperoxidase (MPO) activity and subsequent generation of hypochlorous acid has been associated with the killing of host-invading microorganisms (e.g. bacteria, viruses, and fungi). However, during oxidative stress, high MPO activity can damage host tissue and is linked to several chronic inflammatory conditions. Herein, we describe the development of a novel biaryl, indole-pyrazole series of irreversible mechanism-based inhibitors of MPO. Derived from an indole-containing high-throughput screen hit, optimization efforts resulted in potent and selective 6-substituted indoles with good oral bioavailability and in vivo activity.