N,N'-(Phenylene)dioxamic acids and their esters as antiallergy agents

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Organic Synthesis

Background:

• Allergic reactions pose a significant health burden.
• Development of novel anti-allergic agents is crucial.
• Dioxamic acid derivatives represent a potential class of therapeutics.

Purpose of the Study:

• To synthesize and evaluate novel dialkyl N,N'-(phenylene)dioxamates and their corresponding acids.
• To assess the anti-allergic potential of these compounds in vivo.
• To compare their efficacy with existing anti-allergic drugs like disodium cromoglycate.

Main Methods:

• Synthesis of dialkyl N,N'-(m-phenylene)dioxamates via reaction of m-phenylenediamines with alkyloxalyl chloride.
• Hydrolysis of dioxamates to corresponding dioxamic acids using sodium hydroxide.
• Testing in the rat passive cutaneous anaphylaxis (PCA) assay via intravenous and oral administration.

Main Results:

• N,N'-(m-phenylene)dioxamic acids demonstrated significant anti-allergic activity intravenously, up to 2500 times more potent than disodium cromoglycate.
• Compound 61 (N,N'-(2-chloro-5-cyano-m-phenylene)dioxamic acid) showed 50% inhibition at 0.001 mg/kg.
• Oral administration revealed sustained activity up to 120 minutes, with compound 38 (diethyl N,N'-(2-chloro-5-cyano-m-phenylene)dioxamate) effective at 0.1 mg/kg.

Conclusions:

• Dialkyl N,N'-(phenylene)dioxamates and their corresponding acids are effective anti-allergic agents.
• The m-phenylene derivatives exhibit potent intravenous activity, while both m- and p-phenylene series show oral efficacy.
• These compounds represent promising candidates for the development of new anti-allergy medications.