Identification of Benzoxazin-3-one Derivatives as Novel, Potent, and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists was written by Hasui, Tomoaki;Matsunaga, Nobuyuki;Ora, Taiichi;Ohyabu, Norio;Nishigaki, Nobuhiro;Imura, Yoshimi;Igata, Yumiko;Matsui, Hideki;Motoyaji, Takashi;Tanaka, Toshimasa;Habuka, Noriyuki;Sogabe, Satoshi;Ono, Midori;Siedem, Christopher S.;Tang, Tony P.;Gauthier, Cassandra;De Meese, Lisa A.;Boyd, Steven A.;Fukumoto, Shoji. And the article was included in Journal of Medicinal Chemistry in 2011.Product Details of 58349-01-2 This article mentions the following:
Mineralocorticoid receptor (MR) blockade has come into focus as a promising approach for the treatment of cardiovascular diseases such as hypertension and congestive heart failure. In order to identify a novel class of nonsteroidal MR antagonists that exhibit significant potency and good selectivity over other steroidal hormone receptors, the authors designed a novel series of benzoxazin-3-one derivatives and synthesized them from 6-(7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl)-2H-1,4-benzoxazin-3(4H)-one (I), high-throughput screening (HTS) hit compound Their design was based on a crystal structure of an MR/compound complex and a docking model. In the course of lead generation from I, a 1,2-diaryl framework was characterized as a key structure with high binding affinity. On the basis of scaffold hopping and optimization studies, benzoxazin-3-one derivatives possessing 1-phenyl-3-trifluoromethylpyrazol-5-yl moiety at the 6-position were identified as a novel series of potent and selective MR antagonists. Among these compounds, 6-[1-(4-fluoro-2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-2H-1,4-benzoxazin-3(4H)-one (II) showed highly potent activity and good selectivity and also exhibited a significant antihypertensive effect in deoxycorticosterone acetate-salt hypertensive rats. On the basis of these results, compound II was progressed for further pharmacol. evaluation. In the experiment, the researchers used many compounds, for example, 4-Bromo-2-chloro-6-nitrophenol (cas: 58349-01-2Product Details of 58349-01-2).
4-Bromo-2-chloro-6-nitrophenol (cas: 58349-01-2) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. alpha-Bromoesters are employed in the Reformatsky reaction for the synthesis of beta-hydroxyesters. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.Product Details of 58349-01-2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary