《Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist》 was written by Kim, Seon-Mi; Lee, Minhee; Lee, So Young; Park, Euisun; Lee, Soo-Min; Kim, Eun Jeong; Han, Min Young; Yoo, Taekyung; Ann, Jihyae; Yoon, Suyoung; Lee, Jiyoun; Lee, Jeewoo. Application In Synthesis of Methyl 3-(bromomethyl)benzoateThis research focused onuracil derivative SKI2496 preparation GnRH receptor antagonist pharmacokinetics. The article conveys some information:
The authors developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. Based on in vitro activity and CYP inhibition profile, the authors selected 18a ((R)-4-((2-(3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-5-(4-((5-(trifluoromethyl)-furan-2-yl)methyl)-piperazin-1-yl)-2,3-dihydropyrimidin-1(6H)-yl)-1-phenylethyl)-amino)-butanoic acid, SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clin. advanced compound Considering that 18a exhibited highly potent and selective antagonistic activity toward the hGnRHRs along with favorable pharmacokinetic profiles, the authors believe that 18a may represent a promising candidate for an orally available hormonal therapy. The experimental process involved the reaction of Methyl 3-(bromomethyl)benzoate(cas: 1129-28-8Application In Synthesis of Methyl 3-(bromomethyl)benzoate)
Methyl 3-(bromomethyl)benzoate(cas: 1129-28-8) belongs to organobromine compounds.Depending on the type of carbon to which the bromine is bonded, organic bromide could be alkyl, alkenyl, alkynyl, or aryl. Due to the reactivity of bromide, they are used as potential precursors or important intermediates in organic synthesis. Application In Synthesis of Methyl 3-(bromomethyl)benzoate
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary