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• 19082-52-1 4-phenoxyphenyl acetate 

Relevant academic research and scientific papers

Derivatives of 2-methyl>-1,4-benzodioxan as Orally Active 5-Lipoxygenase Inhibitors

N-Hydroxyureas based on the 1,4-benzodioxan template were prepared from appropriately substituted 1,4-benzodioxan-2-methanols as the key intermediates and evaluated in the in vitro guinea pig polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay for their 5-LO inhibitory activity.Placement of a 7-phenoxy or 7-p-fluorophenoxy substituent resulted in a dramatic increase in in vitro potency.Selected compounds were subsequently assayed in an ex vivo dog model of LTB4 synthesis at a dose of 1.0 mg/kg.The 7-phenoxy derivatives 16 and 17 showed modest duration of action (DA) in this dog model.The 6-regioisomers 21 and 22 were less potent.Replacement of the 7-phenoxy group of 16 with the p-fluorophenoxy moiety enhanced the DA dramatically.Compound 18 (CGS 25667), which had an IC50 value of 100 nM in the in vitro guinea pig 5-LO assay, had a DA of 8.5 h (zileuton, DA = 8.5 h) at the oral dose of 1.0 mg/kg.Optical antipodes (24, 26) of 18 were independently synthesized in high ( >95percent) enantiomeric purity from commercially available optically active glycidyl tosylates and evaluated.In the in vitro assay, the 2S-(-)-enantiomer (24, CGS, 25997, IC50 = 85 nM) was found to be twice as active as the 2R-(+)-counterpart (26, CGS 25998, IC50 = 180 nM).In the ex vivo experiment, 24, which dose dependently inhibited plasma 5-LO activity, was shown to be significantly longer acting than 26, with a DA of 8.4 h when dosed orally at 1.0 mg/kg.

CERTAIN BENZODIOXOLE, BENZODIOXANE AND BENZODIOXEPIN DERIVATIVES USEFUL AS 5-LIPOXYGENASE INHIBITORS

The invention relates to the compounds of the formula wherein each R independently represents hydrogen, lower alkyl, halogen, trifluoromethyl, lower alkoxy, carbocyclic or heterocyclic aryl, carbocyclic or hetero-cyclic aryloxy, carbocyclic or heterocyclic aryl-lower alkyloxy, carbocyclic or heterocyclic aryl-lower alkyl, C3-C7-cycloalkyl-lower alkyloxy, or Cs-Cv-cycloalk-yloxy; n represents 1, 2, 3 or 4; m represents 0, 1 or 2; A represents a direct bond or lower alkylene; X represents oxygen or sulfur; Ri represents hydrogen, acyl, lower alkoxycarbonyl, aminocarbonyl, mono- or di-lower alkylaminocarbonyl, lower alkenylaminocarbonyl, lower alkynylaminocarbonyl, carbocyclic or heterocy-clic aryl-lower alkylaminocarbonyl, carbocyclic or heterocyclic arylaminocarbonyl, C3-C7-cycloalk-ylaminocarbonyl or C3-C7-cycloalkyl-lower al-kylaminocarbonyl; R2 represents lower alkyl, lower alkoxycarbonyl-lower alkyl, C3-C7-cycloalkyl, carbo-cyclic or heterocyclic aryl, carbocyclic or heterocyclic aryl-lower alkyl, C3-C7-cycloalkyl-lower alkyl, amino, mono- or di-lower alkylamino, lower alkenylamino, lower alkynylamino, carbocyclic or heterocyclic aryl-lower alkylamino, carbocyclic or heterocyclic arylamino, C3-C7-cycloalkylamino, C3-C7-cycloalkyl-lower alkylamino, lower alkoxycarbonyl-lower alkyl-amino or lower alkoxy; R3 and R4 independently repre-sent hydrogen or lower alkyl; and pharmaceuticallyacceptable salts thereof; which are useful as 5-lipoxyge-nase inhibitors.