Patent · US Active

Hydrogen peroxide-responsive KEAP1-NRF2 ppi inhibitor prodrug, and preparation method therefor

US12383535B2 · kind B2 · utility

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Key dates

Filing dateNov 16, 2020
Grant dateAug 12, 2025
Priority date
Expiry dateMay 2, 2043

Classification

  • Technology area (CPC C)Chemistry; Metallurgy
  • CPC primaryC07D277/14
  • WIPO fieldPharmaceuticals
  • WIPO sectorChemistry

Abstract

The present application relates to a hydrogen peroxide-responsive Keap1-Nrf2 PPI inhibitor prodrug, and a preparation method therefor. The hydrogen peroxide-responsive Keap1-Nrf2 PPI inhibitor prodrug pro2 has a chemical structure as shown below. By modifying a key carboxyl pharmacophore in a Keap1-Nrf2 inhibitor with a H2O2-responsive thiazolidinone moiety, a novel ROS-responsive antioxidant prodrug pro2 is synthesized. The H2O2 activated prodrug pro2 can simultaneously achieve targeted activation of Nrf2 and enhancement of therapeutic efficacy in the body. The prodrug is based on the concept of ROS activation-ROS clearance therapy, is the first example of a H2O2-responsive prodrug suitable for oral administration, and is expected to be used clinically by virtue of the characteristics of druggability and high targeting ability.

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