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A Tetrazine‐Based Synthesis for Accessing Underutilized Aza‐Indole Analogues

Year: 2025

Type: article

Abstract: Aza-indole functionalities fill an important role in drug discovery. While indoles are considered privileged scaffolds, aza-indoles allow for better pharmacological properties and on-target activities. Synthetic approaches to access aza-indoles are limited, with pyrazolopyridazines being some of the scarcest aza-indoles. To provide access to these underutilized cores, a synthetic approach utilizing a reaction cascade between a protected propargylhydrazine and dichlorotetrazine has been developed. In addition, a variety of methods were developed to access each position on the core for late-stage functionalization. This method offers an expedited synthetic route to a rare aza-indole scaffold with superior physiochemical properties when compared to indole analogues.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.202500751

Authors: Evan Savelson, Katarina A. Selewski, Jetze J. Tepe

Institution: University of Virginia

Language: English

Topic: Synthesis of Indole Derivatives

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $4,640

Funders: National Institutes of Health, National Cancer Institute, National Institute of Neurological Disorders and Stroke