N-(4-Substituted-thiazolyl)oxamic Acid Derivatives, a New Series of Potent, Orally Actve Antiallergy Agents

Article abstract of DOI:10.1021/jm00362a014

A series of N-(4-substituted-thiazolyl)oxamic acid derivatives were synthesized and tested for antiallergy activity in the rat PCA model.These compounds were conveniently prepared by treatment of the appropriate acetophenone with thiourea and iodine or by reaction of the chloroacetylbenzene with thiourea to give the corresponding aminothiazoles; subsequent condensation with ethyloxalyl chloride gave the thiazolyloxamates.Many of the analogues showed a 50percent inhibition at <2 mg/kg po or <0.4 mg/kg iv and were significantly more potent than disodium cromoglycate, which in the rat PCA mode l is orally inactive and gives a 50percent inhibition at 1.2 mg/kg iv.Hydrolysis of the oxamates generally resulted in enhanced activities, while substitution of the phenyl ring with a variety of substituents (e.g.,4-F, 4-OEt, and 4-NHCOCH3) did not significantly enhance the activity of the unsubstituted phenyl derivative.One of the ethanolamine salts, N-<4-(1,4-benzodioxan-6-yl)-2-thiazolyl>oxamic acid ethanolamine salt (61, PRH-836-EA), has been selected for further pharmacological evaluation.