120028-56-0Relevant articles and documents
N- Carboxylic Acids, Hydroxamic Acids, Tetrazoles, and Sulfonyl Carboxamides. Potent Orally Active Leukotriene D4 Antagonists of Novel Structure
Musser, John H.,Kreft, Anthony F.,Bender, Reinhold H. W.,Kubrak, Dennis M.,Grimes, David,et al.
, p. 240 - 245 (2007/10/02)
Four series of N- compounds were prepared as leukotriene D4 (LTD4) antagonists.In the hydroxamic acid series, methyl 3-(2-quinolinylmethoxy)benzeneacetohydroxamate (Wy-48,422, 20) was the most potent inhibitor of LTD4-induced bronchoconstriction with an oral ED50 of 7.9 mg/kg.Compound 20 was also orally inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ED50 of 3.6 mg/kg.In vitro, against LTD4-induced contraction of isolated guinea pig trachea pretreated with indomethacin and 1-cysteine, 20 produced a pKB value of 6.08.In the sulfonyl carboxamide series, N--3-(2-quinolinylmethoxy)-benzamide (Wy-49,353, 30) was the most potent antagonist.Compound 30 orally inhibited both LTD4- and ovalbumin-induced bronchoconstriction with ED50s of 0.4 and 20.2 mg/kg, respectively.In vitro, against LTD4-induced contraction of isolated guinea pig trachea, 30 produced a pKB value of 7.78.In the carboxylic acid series, which served as intermediates for the above two series, 3-(2-quinolinylmethoxy)benzeneacetic acid (Wy-46,016, 5) was the most potent inhibitor of LTD4-induced bronchoconstriction (99percent at 25 mg/kg, intraduodenally); however, the pKB for this compound was disappointing (5.79).In the tetrazole series, the most potent inhibitor was 2-methyl>quinoline (Wy-49,451, 41).The respective inhibitory ED50s were 3.0 mg/kg versus LTD4 and 17.5 mg/kg versus ovalbumin.In the isolated guinea pig trachea, 41 produced a pKB value of 6.70.
2-(phenoxymethyl)-quinazolines as antiallergic and antiinflammatory agents
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, (2008/06/13)
There are disclosed compounds of the formula STR1 wherein STR2 R2 is hydrogen, loweralkyl, loweralkoxy, lower alkoxycarbonyl, trifluoromethyl, nitro, cyano or halo; R3 is hydrogen or loweralkyl; R4 is hydrogen, lower alkyl, --COOR3 or STR3 R5 is lower alkyl, monofluoroloweralkyl, difluoroloweralkyl, polyfluoroloweralkyl, perfluoroloweralkyl or STR4 and the pharmaceutically acceptable salts thereof, and their use in the treatment of leukotriene-mediated naso-bronchial obstructive airpassageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like, and as antiinflammatory agents.