title: N-(4-substituted-thiazolyl)oxamic acid derivatives, a new series of potent, orally active antiallergy agents.
abstract: 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 50% inhibition at less than 2 mg/kg po or less than 0.4 mg/kg iv and were significantly more potent than disodium cromoglycate, which in the rat PCA model is orally inactive and gives a 50% 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.
mesh_terms: D000818:Animals; D006967:Hypersensitivity / Q000188:drug therapy*; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D013055:Spectrophotometry, Infrared; D013844:Thiazoles / Q000138:chemical synthesis* / Q000627:therapeutic use
chemical_list: D013844:Thiazoles; C038725:N-(4-(1,4-benzodioxan-6-yl)-2-thiazolyl)oxamic acid