135199-38-1Relevant articles and documents
Synthesis of diaryl ethers, diaryl thioethers, and diarylamines mediated by potassium fluoride-alumina and 18-crown-6: Expansion of scope and utility
Sawyer, J. Scott,Schmittling, Elisabeth A.,Palkowitz, Jayne A.,Smith III, William J.
, p. 6338 - 6343 (2007/10/03)
An efficient alternative to the Ullmann ether synthesis of diaryl ethers, diaryl thioethers, and diarylamines involving the S(N)Ar addition of a phenol, thiophenol, or aniline to an appropriate aryl halide, mediated by potassium-fluoride alumina and 18-crown-6 in acetonitrile or DMSO, is described. Expansion of the reaction conditions to include DMSO as solvent has resulted in a far greater range of substitution patterns permitted on the electrophile. For example, it was found that electronically unfavorable 3- chlorobenzonitrile could be condensed with 3-methoxyphenol to form the corresponding diaryl ether in 66% yield, a combination not normally amenable to Ullmann coupling. Electron-withdrawing groups present on the electrophile may be as diverse as nitro, cyano, formyl, acetyl, ester, amide, and even aryl. The method features a simple reaction procedure that provides products in generally good to excellent purified yields.
Design, Synthesis, and Pharmacological Evaluation of Potent Xanthone Dicarboxylic Acid Leukotriene B4 Receptor Antagonists
Jackson, William T.,Boyd, Robert J.,Froelich, Larry L.,Gapinski, D. Mark,Mallett, Barbara E.,Sawyer, J. Scott
, p. 1726 - 1734 (2007/10/02)
In an effort to develop increasingly potent and specific leukotriene B4(LTB4) receptor antagonists, several xanthone dicarboxylic acids were synthesized and evaluated.Two separate synthetic routes were used to construct a xanthone nucleus containing a regiospecific orientation of each carboxylic acid pharmacophore.These compounds represent the major conformationally-restricted analogues of benzophenone dicarboxylic acids previously shown to antagonize the activation of human neutrophils by LTB4.The most potent agent was compound 32, which inhibited the specific binding of LTB4 to receptors on intact human neutrophils (IC50, 6.2 +/- 0.1 nM), LTB4-induced luminol-dependent chemiluminescence (IC50, 55 +/- 11 nM), aggregation (IC50, 133 +/- 42 nM), and chemotaxis (IC50, 899 +/- 176 nM).The compound was a poor antagonist of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced chemiluminescence (IC50, 1599 +/- 317 nM) and aggregation (IC50, 2166 +/- 432 nM), indicating specificity in the inhibition of LTB4-stimulated events.Compound 32(LY210073), which was completely devoid of agonist activity, appears to be one of the strongest inhibitors of LTB4 receptor binding reported so far.
