YK-4-250, A Synthetic Telmisartan-Tempol Conjugate: Crystal Structure of a Stabilized Free Radical Containing An Angiotensin AT₁ Receptor Inhibitor

Authors

• Simon Friedrich, Virginia Commonwealth University
• Yali Kong, Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
• Faik N. Musayev, Virginia Commonwealth University
• Milton L. Brown, Virginia Commonwealth University
• B. Frank Gupton, Virginia Commonwealth University

ORCID

0009-0008-7575-2043 (Kong)

Document Type

Article

Publication Date

2026

DOI

10.1107/S2053229626007242

Publication Title

Acta Crystallographica Section C: Structural Chemistry

Volume

82

Issue

9

Pages

547-552

Abstract

We report the first crystal structure of the telmisartan-tempol conjugate 2,2,6,6-tetramethyl-1-(λ'-oxidaneyl)piperidin-4-yl 4'-[(1,7'-dimethyl-2'-propyl-1H,3'H-[2,5'-bibenzo[d]imidazol]-3'-yl)methyl]-[1,1'-biphenyl]-2-carboxylate free radical (YK-4-250, C₄₂H₄₆N₅O₃), a dual-function inhibitor designed to target both the angiotensin II type 1 receptor (AT₁R) and reactive oxygen species (ROS). Structural analysis reveals a unique crystal architecture in which the nitroxide radical is stabilized within a sterically protected environment while preserving the telmisartan pharmacophore essential for high-affinity receptor antagonism. YK-4-250 is a novel small-molecule conjugate of telmisartan and tempol that incorporates a catalytic stabilized nitroxide radical and was rationally designed to mitigate gastrointestinal acute radiation syndrome (GI-ARS).

Rights

© 2026 The Authors.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Original Publication Citation

Friedrich, S., Kong, Y., Musayev, F. N., Brown, M. L., & Gupton, B. F. (2026). YK-4-250, a synthetic telmisartan-tempol conjugate: Crystal structure of a stabilized free radical containing an angiotensin AT(1) receptor inhibitor. Acta Crystallographica Section C: Structural Chemistry, 82, 547-552. https://doi.org/10.1107/s2053229626007242

Repository Citation

Friedrich, S., Kong, Y., Musayev, F. N., Brown, M. L., & Gupton, B. F. (2026). YK-4-250, a synthetic telmisartan-tempol conjugate: Crystal structure of a stabilized free radical containing an angiotensin AT(1) receptor inhibitor. Acta Crystallographica Section C: Structural Chemistry, 82, 547-552. https://doi.org/10.1107/s2053229626007242