YK-4-250, a synthetic telmisartan–tempol conjugate: crystal structure of a stabilized free radical containing an angiotensin AT 1 receptor inhibitor

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-1 H ,3′ H -[2,5′-bibenzo[ d ]imidazol]-3′-yl)methyl]-[1,1′-biphenyl]-2-carboxylate free radical (YK-4-250, C 42 H 46 N 5 O 3 ), a dual-function inhibitor designed to target both the angiotensin II type 1 receptor (AT 1 R) 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).