- Design and discovery of 2-oxochromene derivatives as liver X receptor β-selective agonists
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In an attempt to molecularly design liver X receptor (LXR) β-selective agonists, we discovered that the combination of the 2-oxochromene moiety (head) and the imidazoline-2,4-dione moiety (tail) plays an important role in the expression potency and select
- Matsuda, Takayuki,Okuda, Ayumu,Watanabe, Yuichiro,Miura, Tohru,Ozawa, Hidefumi,Tosaka, Ayako,Yamazaki, Koichi,Yamaguchi, Yuki,Kurobuchi, Sayaka,Koura, Minoru,Shibuya, Kimiyuki
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supporting information
p. 1274 - 1278
(2015/03/14)
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- CHROMEN-2-ONE DERIVATIVES
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A compound of formula (I), wherein R1, R2, R3, R4, R5, and ring A are as defined in the specification, processes for their production, their uses, in particular in transplantation, and pharmaceutical
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Page/Page column 19
(2010/11/28)
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- BENZYLIDENE RHODANINES
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This invention provides novel benzylidene rhodanines which are useful as agents in treating or preventing conditions associated with . beta.-amyloid peptide. This invention further provides methods of treating or preventing Alzheimer's Disease which comprises administering to a mammal in need thereof an effective amount of one or more of the benzylidene rhodanines of the present invention.
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- Leukotriene antagonists for use in the treatment or prevention of alzheimer's disease
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This invention provides methods for the treatment or prevention of Alzheimer's disease which comprises administering to a mammal in need thereof an effective amount of a compound having activity as a leukotriene antagonist.
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- 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
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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.
- Sawyer,Bach,Baker,Baldwin,Borromeo,Cockerham,Fleisch,Floreancig,Froelich,Jackson,Marder,Palkowitz,Roman,Saussy Jr.,Schmittling,Silbaugh,Spaethe,Stengel,Sofia
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p. 4411 - 4432
(2007/10/03)
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- SUBSTITUTED PHENYL PHENOL LEUKOTRIENE ANTAGONISTS
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Antagonists having a substituted phenyl phenol or a substituted phenolic biphenyl structure, and various derivatives thereof, are specific leukotriene antagonists. Their structures, use and synthesis are disclosed. Also, pharmaceutical formulations are disclosed for use in applications treating diseases or conditions characterized by excessive release of leukotriene B 4, one of the metabolites of arachidonic acid.The primary LTB 4 antagonistic structures are represented as: STR1
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- USE OF PLA2 INHIBITORS AS TREATMENT FOR ALZHEIMER'S DISEASE
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This invention provides methods for the treatment or prevention of Alzheimer's disease in a mammal which comprises administering to a mammal in need thereof an effective amount of an inhibitor of phospholipase A2. This invention also provides a series of compounds which are useful as inhibitors of phospholipases A2, especially cytosolic phospholipase A2.
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- LEUKOTRIENE B4 ANTAGONISTS
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This invention relates to compounds of Formula I and the stereoisomers and pharmaceutically acceptable salts thereof STR1 wherein R is alkyl, alkenyl, alkynyl, or cycloalkylalkyl;R 1 is alkyl; R 2 is hydrogen, alkyl;R 6 is alkyl;
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- LEUKOTRIENE B4 ANTAGONISTS
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This invention provides certain 1,2,4,5 substituted benzene derivatives containing "acid" substituents derived from cyclic or heterocyclic moieties. These unique compounds are leukotriene B 4 antagonists and formulations of these derivatives, and a method of using these derivatives for the treatment of conditions characterized by an excessive release of leukotrienes. "
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- Leukotriene B4 antagonists
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This invention relates to compounds of Formula I and the stereoisomers and pharmaceutically acceptable salts thereof STR1 wherein R is alkyl, alkenyl, alkynyl, or cycloalkylalkyl; R1 is alkyl; R2 is hydrogen or alkyl; R6 i
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- A Convenient Synthesis of 2-Alkyl-mono-O-alkylated and 2-Alkyl Resorcinols
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The title C,O-dialkylated resorcinols have seldom been prepared.We have developed a practical synthesis of this class of compounds starting with cyclohexane-1,3-dione.The key features of the synthesis are mono-O-alkylation of a 2-alkyl cyclohexane-1,3-dio
- Stealey, M.A.,Shone, R.L.,Miyano, M.
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p. 1869 - 1876
(2007/10/02)
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- Hydroxyacetophenone-derived antagonists of the peptidoleukotrienes
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Considerations of the possible similarities between leukotriene D4 and its prototypical antagonist, FPL 55712, led to the development of a new series of leukotriene antagonists incorporating a hydroxyacetophenone group (e.g., the toluic acids 1
- Brown,Bersntein,Cronk,Dossett,Hebbel,Maduskuie Jr.,Shapiro,Vacek,Yee,Willard,Krell,Snyder
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p. 807 - 826
(2007/10/02)
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