In 2022,Guan, Xianghong; Cheryala, Narsihmulu; Karim, Rezaul Md.; Chan, Alice; Berndt, Norbert; Qi, Jun; Georg, Gunda I.; Schonbrunn, Ernst published an article in Journal of Medicinal Chemistry. The title of the article was 《Bivalent BET Bromodomain Inhibitors Confer Increased Potency and Selectivity for BRDT via Protein Conformational Plasticity》.Application In Synthesis of Ethyl 4-bromobutyrate The author mentioned the following in the article:
Bromodomain and extraterminal domain (BET) proteins are important regulators of gene transcription and chromatin remodeling. BET family members BRD4 and BRDT are validated targets for cancer and male contraceptive drug development, resp. Due to the high structural similarity of the acetyl-lysine binding sites, most reported inhibitors lack intra-BET selectivity. We surmised that protein-protein interactions induced by bivalent inhibitors may differ between BRD4 and BRDT, conferring an altered selectivity profile. Starting from nonselective monovalent inhibitors, we developed cell-active bivalent BET inhibitors with increased activity and selectivity for BRDT. X-ray crystallog. and solution studies revealed unique structural states of BRDT and BRD4 upon interaction with bivalent inhibitors. Varying spacer lengths and sym. vs unsym. connections resulted in the same dimeric states, whereas different chemotypes induced different dimers. The findings indicate that the increased intra-BET selectivity of bivalent inhibitors is due to the differential plasticity of BET bromodomains upon inhibitor-induced dimerization. The results came from multiple reactions, including the reaction of Ethyl 4-bromobutyrate(cas: 2969-81-5Application In Synthesis of Ethyl 4-bromobutyrate)
Ethyl 4-bromobutyrate(cas: 2969-81-5) belongs to bromides. Most organobromine compounds, like most organohalide compounds, are relatively nonpolar. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents.Application In Synthesis of Ethyl 4-bromobutyrate
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary