In 2022,Georgakopoulos, Nikolaos; Talapatra, Sandeep; Dikovskaya, Dina; Dayalan Naidu, Sharadha; Higgins, Maureen; Gatliff, Jemma; Ayhan, Aysel; Nikoloudaki, Roxani; Schaap, Marjolein; Valko, Klara; Javid, Farideh; Dinkova-Kostova, Albena T.; Kozielski, Frank; Wells, Geoffrey published an article in Journal of Medicinal Chemistry. The title of the article was 《Phenyl Bis-Sulfonamide Keap1-Nrf2 Protein-Protein Interaction Inhibitors with an Alternative Binding Mode》.Category: amides-buliding-blocks The author mentioned the following in the article:
Inhibitors of Kelch-like ECH-associated protein 1 (Keap1) increase the activity of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) by stalling its ubiquitination and degradation This enhances the expression of genes encoding proteins involved in drug detoxification, redox homeostasis, and mitochondrial function. Nrf2 activation offers a potential therapeutic approach for conditions including Alzheimer’s and Parkinson’s diseases, vascular inflammation, and chronic obstructive airway disease. Non-electrophilic Keap1-Nrf2 protein-protein interaction (PPI) inhibitors may have improved toxicity profiles and different pharmacol. properties to cysteine-reactive electrophilic inhibitors. Here, we describe and characterize a series of Ph bis-sulfonamide PPI inhibitors that bind to Keap1 at submicromolar concentrations Structural studies reveal that the compounds bind to Keap1 in a distinct “”peptidomimetic”” conformation that resembles the Keap1-Nrf2 ETGE peptide complex. This is different to other small mol. Keap1-Nrf2 PPI inhibitors, including bicyclic aryl bis-sulfonamides, offering a starting point for new design approaches to Keap1 inhibitors. The experimental part of the paper was very detailed, including the reaction process of 2-Bromoacetamide(cas: 683-57-8Category: amides-buliding-blocks)
2-Bromoacetamide(cas: 683-57-8) can be used in preparation of (2-carbamoylmethoxy-5-chloro-benzyl)-carbamic acid tert-butyl ester. It was aslo used as precursor to dehydropeptidase I inactivator.Category: amides-buliding-blocks
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics