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.

公开(公告)号：US20210061814A1

公开(公告)日：2021-03-04

申请号：US16924037

申请日：2020-07-08

Applicant: St. Louis College of Pharmacy ,  University of Southern California ,  The University of North Carolina at Chapel Hill ,  Memorial Sloan Kettering Cancer Center ,  University of Florida Research Foundation, Incorporated ,  Memorial Sloan Kettering Cancer Center

Inventor： Susruta MAJUMDAR ,  Vsevolod KATRITCH ,  Bryan ROTH ,  JAY MCLAUGHLIN ,  Saheem ZAIDI ,  Gavril W. PASTERNAK ,  Rajendra UPRETY

IPC: C07D489/00 ,  C07D221/28

Abstract: In some aspects, the present disclosure provides compounds of the formula: wherein the variables are as defined herein. In some embodiments, these compounds may be used to reduce the pain of a patient. These compounds may be used in pain relief and show an improved pharmaceutical profile relative to other commonly used opiates and opioid derivatives.