Work

Accelerated Synthesis of Novel Indole-3-Sulfonamides Leveraging High-Throughput Experimentation

Year: 2026

Type: article

Abstract: Non-nucleoside reverse transcriptase inhibitors are key compounds of current antiretroviral therapy for people living with human immunodeficiency virus (HIV). Indole-3-sulfonamides have demonstrated good biological profile against HIV. Here we describe a high-throughput experimentation (HTE)-compatible route to access indole-3-sulfonamides through a selective activation of the S-N bond of a primary indole-3-sulfonamide. This selective activation strategy enables efficient installation of diverse amine substituents with broad functional-group tolerance. Cheminformatic tools were integrated into the workflow to analyze accessible chemical space, prioritize amine nucleophiles, and guide building-block selection to maximize structural diversity. The protocol rapidly delivered a set of novel indole-3-sulfonamide analogs, demonstrating practical applicability and efficiency for medicinal chemistry campaigns.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.6c00331

Authors: Olivia P. Bercher, Kaitlin Lupinacci, Michael J. Breslin, Abdellatif El Marrouni

Institution: Merck & Co., Inc., Rahway, NJ, USA (United States)

Language: English

Topic: Synthesis of Indole Derivatives

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7203707888