153607-77-3Relevant academic research and scientific papers
Substituted (Pyridylmethoxy)naphthalenes as potent and orally active 5- Lipoxygenase inhibitors: Synthesis, biological profile, and pharmacokinetics of L-739,010
Hamel, Pierre,Riendeau, Denis,Brideau, Christine,Chan, Chi-Chung,Desmarais, Sylvie,Delorme, Daniel,Dubé, Daniel,Ducharme, Yves,Ethier, Diane,Grimm, Erich,Falgueyret, Jean-Pierre,Guay, Jocelyne,Jones, Tom R.,Kwong, Elizabeth,McAuliffe, Malia,McFarlane, Cyril S.,Piechuta, Hanna,Roumi, Marie,Tagari, Philip,Young, Robert N.,Girard, Yves
, p. 2866 - 2875 (2007/10/03)
Dioxabicyclooctanyl naphthalenenitriles have been reported as a class of potent and nonredox 5-lipoxygenase (5-LO) inhibitors. These bicyclo derivatives were shown to be metabolically more stable than their tetrahydropyranyl counterparts but were not well orally absorbed. Replacement of the phenyl ring in the naphthalenenitrile 1 by a pyridine ring leads to the potent and orally absorbed inhibitor 3g (L-739,010, 2-cyano-4-(3-furyl)- 7-[[6-[3-(3-hydroxy-6,8-dioxabicyclo[3.2.1]octanyl)]-2- pyridyl]methoxy]naphthalene). Compound 3g inhibits 5-HPETE production by human 5-LO and LTB4 biosynthesis by human PMN leukocytes and human whole blood (IC50s of 20, 1.6, and 42 nM, respectively). Derivative 3g is orally active in the rat pleurisy model (inhibition of LTB4, ED50 = 0.3 mg/kg) and in the anesthetized dog model (inhibition of ex vivo whole blood LTB4 and urinary LTB4, ED50 = 0.45 and 0.23 μg/kg/min, respectively, iv infusion). In addition, 3g shows excellent functional activity against ovalbumin-induced dyspnea in rats (60% inhibition at 0.5 mg/kg, 4 h pretreatment) and Ascaris-induced bronchoconstriction in conscious sheep (50% and >85% inhibition in early and late phases, respectively at 2.5 μg/kg/min, iv infusion) and, more particularly in the conscious antigen sensitive squirrel monkey model (53% inhibition of the increase in R(L) and 76% in the decrease of C(dyn), at 0.1 mg/kg, po). In rats and dogs, 3g presents excellent pharmacokinetics (estimated half-lives of 5 and 16 h, respectively) and bioavailabilities (26% and 73% when dosed as its hydrochloride salt at doses of 20 and 10 mg/kg, respectively, in methocel suspension). Based on its overall biological profile, compound 3g has been selected for preclinical animal toxicity studies.
Synthesis biological and biological evaluation of some acyclic pyridine C-nucleosides. Part two
Van Hemel, Johan,Esmans, Eddy L.,De Groot, Alex,Dommisse, Roger A.,Balzarini, Jan M.,De Clercq, Erik D.
, p. 1203 - 1221 (2007/10/03)
3-Bromo-5-(2-hydroxyethylthiomethyl)pyridine (7) was synthesized by reaction of 3-bromo-5-chloromethylpyridine hydrochloride (6) with the mono sodium salt of 2-mercaptoethanol. 3-Bromo-5-hydroxymethylpyridine (10) was, after protection as a silyl ether, c
Phenylnaphthalene hydroxy acids
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, (2008/06/13)
Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular
Phenylnaphthalene lactones as inhibitors of leukotriene biosynthesis
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, (2008/06/13)
Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular
Heteroarylnaphthalenes as inhibitors of leukotriene biosynthesis
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, (2008/06/13)
Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis and allograft rejection and in preventing the formation of atherosclerotic plaques.
Heteroaryl cinnamic acids as inhibitors of leukotriene biosynthesis
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, (2008/06/13)
Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection and in preventing the formation of atherosclerotic plaques.
Heteroarylnaphthalene hydroxy acids as inhibitors of leukotriene biosynthesis
-
, (2008/06/13)
Compounds having the formula I: STR1 are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection and in preventing the formation of atherosclerotic plaques.
