113836-41-2

Upstream product

• 113836-40-1 11-hydroxy-2-<2-<(triphenylmethyl)oxy>ethyl>-6,11-dihydroxydibenzoxepin 
• 56427-65-7 11-hydroxy-2-(2-hydroxyethyl)-6,11-dihydrodibenz[b,e]oxepin 
• 55453-87-7 isoxepac 

Downstream Products

• 19070-16-7 3-(N,N-dimethylamino)propylmagnesium chloride 
• 140439-66-3 11-(3-dimethylaminopropyl)-11-hydroxy-2-(2-triphenylmethyloxyethyl)-6,11-dihydrodibenz[b,e]oxepin 

Relevant academic research and scientific papers

DIBENZ[B,E]OXEPIN DERIVATIVE AND PHARMACEUTICAL COMPOSITIONS THEREOF

Novel dibenz[b,e]oxepin derivatives are employed in the treatment and control of allergic conditions such as allergic asthma and also employed in the treatment of inflammation.

Synthesis and Antiallergic Activity of 11-(Aminoalkylidene)-6,11-dihydrodibenzoxepin Derivatives

A new series of 11-substituted 6,11-dihydrodibenzoxepin-2-carboxylic acid derivatives was synthesized and demonstrated to be orally active antiallergic agents.These compounds are structurally related to 1 (KW-4994), which we had reported previously to be a new antiallergic agents.Most compounds synthesized exhibited potent inhibitory effects on 48-h homogolous passive cutaneous anaphylaxis (PCA) in rats and on IgG1-mediated bronchoconstriction in guinea pigs.Additionally, compounds possessing a terminal carboxyl group at the 2-position of the dibenzoxepin ring system exhibited inhibitory effects on specific pyrilamine binding to guinea pig cerebellum histamine H1 receptors, whereas these demonstrated negligible effects on specific QNB binding to rat striatum muscarinic acetylcholine M1 receptors.Structure-activity relationship studies revealed that the following key elements were required for enhanced antiallergic activities: (1) a 3-(dimethylamino)propylidene group as the side chain at the 11-position, (2) a terminal carboxyl moiety at the 2-position, and (3) a dibenzoxepin ring system.Among the compounds synthesized, (Z)-11--6,11-dihydrodibenzoxepin-2-acetic acid hydrochloride (16) was selected for further evaluation.It had an ED50 value of 0.049 mg/kg po in the PCA test in rats and an ID50 value of 0.030 mg/kg po in inhibiting anaphylactic bronchoconstriction in guinea pigs.Furthermore, it had a Ki value of 16 +/- 0.35 nM for the histamine H1 receptor, while it exhibited negligible CNS side effects up to a dose of 600 mg/kg po.Compound 16 is now under clinical evaluation as KW-4679.