161386-58-9

Upstream product

• 5335-82-0 1,1'-(disulfane-1,2-diylbis(4,1-phenylene))bis(ethan-1-one) 
• 403-42-9 1-(4-fluorophenyl)ethanone 
• 156538-36-2 bis<4-(2-methyl-1,3-dioxolan-2-yl)phenyl> disulfide 
• 156538-37-3 4'-(4-bromothien-2-ylthio)acetophenone ethylene acetal 
• 1778-09-2 4-(Methylthio)acetophenone 
• 3814-20-8 4-mercaptoacetophenone 
• 161386-57-8 4'-[4-(2-hydroxy-1-tetrahydropyran-2-yloxyprop-2-yl)thien-2-ylthio]acetophenone ethylene acetal 

Relevant academic research and scientific papers

Chiral Dioxolane Inhibitors of Leukotriene Biosynthesis: Structure-Activity Relationships and Syntheses Using Asymmetric Dihydroxylation

1,3-Dioxolanes have been described as chiral inhibitors of 5-lipoxygenase (5LO).In the present work, this series has been developed further to provide agents which showed comparable or superior potency in vivo to ZD2138, a methoxytetrahydropyran inhibitor of 5LO, which is currently undergoing clinical evaluation.An asymmetric synthesis was developed to these dioxolanes based on asymmetric dihydroxylation. (S)-N-Methyl-4'-thio>acetanilide ((S)-10d) inhibited leukotriene B4 (LTB4) synthesis in A23187-stimulated human whole blood in vitro with IC50 0.039μM, 25-fold more potent than (R)-10d.In vivo, (S)-10d inhibited LTB4 synthesis by 70percent in zymosan-inflamed air pouch exudate in rat 10 h after an oral dose of 1.5 mg/kg.Structure-activity relationship considerations suggested that the dioxolane and methoxytatrahydropyran series are related, a conclusion which can be supported by molecular modeling.

OXIME DERIVATIVES

The invention concerns oxime derivatives of the formula I wherein R4 includes hydrogen, carboxy, carbamoyl, amino, cyano, trifluoromethyl, (1-4C)alkylamino, di(1-4C)alkylamino and (1-4C)alkyl; RS includes hydrogen, (1-4C)alkyl, (3-4C)alkeny1,(3-4C)alkynyl, (2-5C)alkanoyl, halogeno-(2-4-C)alkyl and hydroxy-(2-4C)alky1;Arl is phenylene or a hetercaryl diradical; Al is a direct link to XI, or Al is (1-4C)alkylene; XI is oxy, thio, sulphinyl or sulphonyl; Ar2 is phenylene or a heteroaryl diradical; RI is (1-4C)alkyl, (3-4C)alkenyl or (3-4C)alkyny1; and R2 and R3 together form a group of the formula -A2. X2-A3- which together with the carbon atom to which A2 and A3 are attached define a ring having 5 or 6 ring atoms, wherein each of A2 and A3 is (1-3C)alkylene and X2 is oxy, thio, sulphinyl, sulphonyl or imino; or a pharmaceutically-acceptable sah thereof; processes for their manufacture; pharmaceutical compositions containing them and their use as 5-lipoxygenase inhibitors.