93114-94-4Relevant academic research and scientific papers
Photochemistry of Substituted 4,4-Dimethoxy-2,5-Cyclohexadienones
Hong, Fang-Tsao,Lee, Kung-Shing,Tsai, Yow-Fu,Liao, Chun-Chen
, p. 1 - 12 (2007/10/03)
4,4-Dimethoxy-2,5-cyclohexadienones 9-14 were prepared from the corresponding hydroquinone monomethyl ethers by oxidation with thallium trinitrate in methanol. Irradiation of solutions of 9-13 in methanol with a broad band of UV light centered at 350 nm in a Rayonet reactor afforded 2-cyclopentenone derivatives 15-19 in moderate to excellent yields, whereas irradiation of 14 in methanol gave phenol 8 along with other unidentified products. Irradiation of 11-14 in benzene yielded substituted phenols. The plausible reaction pathways for the product formation are discussed.
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
Sawyer,Bach,Baker,Baldwin,Borromeo,Cockerham,Fleisch,Floreancig,Froelich,Jackson,Marder,Palkowitz,Roman,Saussy Jr.,Schmittling,Silbaugh,Spaethe,Stengel,Sofia
, p. 4411 - 4432 (2007/10/03)
Structural derivatives of LY255283 have been studied as receptor antagonists of leukotriene B4. Substitution of the 2-hydroxyacetophenone subunit of 1 (LY255283) with a 2-arylphenol group provided entry into several new series that feature various mono- and diacidic core functionality. These new analogues, the subject of a broad structure-activity investigation, displayed significantly increased in vitro and in vive activity as receptor antagonists of LTB4. A series of diaryl ether carboxylic acids demonstrated especially interesting activity and led to the discovery of compound 43b, 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 ± 4.6 nM) and guinea pig lung membranes (IC50 = 6.6 ± 0.71 nM), inhibition of LTB4-induced expression of the CD11b/CD18 receptor on human neutrophils (IC50 = 3.3 ± 0.81 nM), and inhibition of LTB4-induced contraction of guinea pig lung parenchyma (pK(B) = 8.7 ± 0.16). In vivo, 43b demonstrated potent activity in inhibiting LTB4-induced airway obstruction in the guinea pig when dosed by the oral (ED50 = 0.40 mg/kg) or intravenous (ED50 = 0.014 mg/kg) routes. A specific LTB4 receptor antagonist, 43b had little effect on inhibiting contractions of guinea pig lung parenchyma induced by leukotriene D4 (LTD4), histamine, carbachol, or U46619. Compound 43b has been chosen as a clinical candidate and is currently in phase I studies for a variety of inflammatory diseases.
