N,N'-(Phenylene)dioxamic acids and their esters as antiallergy agents.
A series of dialkyl N,N'-(m-phenylene)dioxamates was synthesized by treatment of the requisite m-phenylenediamines with an alkyloxalyl chloride in the presence of triethylamine. Hydrolysis with sodium hydroxide solution gave the corresponding N,N'-(m-phenylene)dioxamic acids. Several N,N'-(p-phenylene)dioxamic acids were synthesized also in the same manner starting with the requisite p-phenylenediamines. These compounds were tested in the rat passive cutaneous anaphylaxis (PCA) assay. When tested iv, activity was found in the N,N'-(m-phenylene) dioxamic acids up to 2500 times that shown by disodium cromoglycate [50% inhibition at 0.001 mg/kg for N,N'-(2-chloro-5-cyano-m-phenylene)dioxamic acid (compound 61)]. Oral activity was seen in this series of compounds with duration of activity up to 120 min. Oral activity was detected in diethyl N,N'-(2-chloro-5-cyano-m-phenylene)dioxamate (compound 38) at levels of drug as low as 0.1 mg/kg.
D000284:Administration, Oral; D000596:Amino Acids / Q000138:chemical synthesis*; D000818:Animals; D004205:Cromolyn Sodium / Q000494:pharmacology; D007275:Injections, Intravenous; D010072:Oxamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D051381:Rats; D013329:Structure-Activity Relationship
D000596:Amino Acids; D004205:Cromolyn Sodium; D010072:Oxamic Acid