Synthetic and Structure/Activity Studies on Acid-Substituted 2-Arylphenols: Discovery of 2-[2-Propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]- propoxy]phenoxy]benzoic Acid, a High-Affinity Leukotriene B4 Receptor Antagonist was written by Sawyer, J. Scott;Bach, Nicholas J.;Baker, S. Richard;Baldwin, Ronald F.;Borromeo, Peter S.;Cockerham, Sandra L.;Fleisch, Jerome H.;Floreancig, Paul;Froelich, Larry L.. And the article was included in Journal of Medicinal Chemistry in 1995.Category: bromides-buliding-blocks This article mentions the following:
Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B4. Substitution of the 2-hydroxyacetophenone subunit of 1-[5-Ethyl-2-hydroxy-4-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]phenyl]ethanone (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogs, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vivo activity as receptor antagonists of LTB4. A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]propoxy]phenoxy]benzoic acid (LY293111), a 2-arylphenol-substituted diaryl ether carboxylic acid which displayed potent binding to human neutrophils (IC50 = 17 鍗?4.6 nM) and guinea pig lung membranes (IC50 = 6.6 鍗?0.71 nM), inhibition of LTB4-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 = 3.3 鍗?0.81 nM), and inhibition of LTB4-induced contraction of guinea pig lung parenchyma (pKB = 8.7 鍗?0.16). 801Vivo, LY293111 demonstrated potent activity in inhibiting LTB4-induced airway obstruction in the guinea pig when dosed by the oral (ED50 = 0.40 mg/kg) or i.v. (ED50 = 0.014 mg/kg) routes. A specific LTB4 receptor antagonist, LY293111 had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D4 (LTD4), histamine, carbachol, or U46619. LY293111 was chosen as a clin. candidate and is currently in phase I studies for a variety of inflammatory diseases. In the experiment, the researchers used many compounds, for example, Methyl 2-bromo-4-fluorobenzoate (cas: 653-92-9Category: bromides-buliding-blocks).
Methyl 2-bromo-4-fluorobenzoate (cas: 653-92-9) 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. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary