Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities was written by Cioffi, Christopher L.;Muthuraman, Parthasarathy;Raja, Arun;Varadi, Andras;Racz, Boglarka;Petrukhin, Konstantin. And the article was included in Journal of Medicinal Chemistry in 2020.Application In Synthesis of Methyl 3-bromo-4-fluorobenzoate This article mentions the following:
Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analog I possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding. In the experiment, the researchers used many compounds, for example, Methyl 3-bromo-4-fluorobenzoate (cas: 82702-31-6Application In Synthesis of Methyl 3-bromo-4-fluorobenzoate).
Methyl 3-bromo-4-fluorobenzoate (cas: 82702-31-6) belongs to organobromine compounds. Most of the natural organobromine compounds are produced by marine organisms, and several brominated metabolites with antibacterial, antitumor, antiviral, and antifungal activity have been isolated from seaweed, sponges, corals, molluscs, and others. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Application In Synthesis of Methyl 3-bromo-4-fluorobenzoate
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary