公开(公告)号：US20230111856A1

公开(公告)日：2023-04-13

申请号：US17908203

申请日：2021-03-02

Applicant: UNIVERSITY OF SOUTHERN CALIFORNIA

Inventor： Vsevolod KATRITCH ,  Valery V. FOKIN ,  Saheem ZAIDI ,  Joice THOMAS

IPC: C07D489/08 ,  A61P11/16

Abstract: The first selective SuFEx antagonists to μ-opioid receptors (MOR) were developed by functionalizing an opioid scaffold with an SO2—F warhead. Our model, based on a MOR structure with antagonist β-FNA, indicates the naloxone carbonyl as an advantageous point for derivatization as it is chemically accessible and is not involved in interaction with receptors. Of the three accessible Tyr residues in MOR pocket, Tyr77, Tyr130 and Tyr150, Tyr150 in proximity to the carbonyl of the docked naloxone was selected as a target, which resulted in the development of highly potent antagonists.