HPLC of Formula: 683-57-8In 2021 ,《Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds》 was published in Journal of Medicinal Chemistry. The article was written by Pallesen, Jakob S.; Narayanan, Dilip; Tran, Kim T.; Solbak, Sara M. Oe.; Marseglia, Giuseppe; Soerensen, Louis M. E.; Hoej, Lars J.; Munafo, Federico; Carmona, Rosa M. C.; Garcia, Anthony D.; Desu, Haritha L.; Brambilla, Roberta; Johansen, Tommy N.; Popowicz, Grzegorz M.; Sattler, Michael; Gajhede, Michael; Bach, Anders. The article contains the following contents:
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-mol. Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallog. to bind in the Keap1 Kelch binding pocket. Two hits were merged into pyrazole I with a 220-380-fold stronger affinity (Ki = 16μM) relative to the parent fragments. Systematic optimization resulted in several novel analogs with Ki values of 0.04-0.5μM, binding modes determined by X-ray crystallog., and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI. After reading the article, we found that the author used 2-Bromoacetamide(cas: 683-57-8HPLC of Formula: 683-57-8)
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.HPLC of Formula: 683-57-8
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics