N-(4-Substituted-thiazolyl)oxamic acid derivatives, 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.

Synthesis and Characterization of Novel 1,3-Thiazole and 2-Amino-1,3,4-Thiadiazole Derivatives

“…Thiazole and thiadiazole derivatives are known to exhibit various biological activities, such as anti-allergy [4], antihypertensive [5], anti-in-flammatory [6][7], anti-schizophrenia [8], antifungal [9], antibacterial [10], antimicrobial [11][12][13], analgesic [14], anti-HIV [15], anticonvulsant [16], antidepressant [17], and anti-cancer [18][19][20][21] properties. Other uses of heterocyclic compounds containing nitrogen and sulfur include manufacturing biocides, dyes [22][23][24], and plant-growth regulators [25].…”

Crystal structure of 2-(bis(4-methoxyphenyl)amino)-2-oxoacetic acid, C16H15NO5

“…Aryl oxamic acid derivatives have various interesting applications [4][5][6][7][8]. In addition, aryl oxamic acids can be used as intermediates for the synthesis of various classes of compounds including heterocycles [9][10][11][12].…”

Synthesis, Anticancer and Antioxidant Activity of Novel 2,4-Disubstituted Thiazoles

“…Thiazole derivatives have been extensively studied and so far, a variety of biological activities have been reported, for a large number of their derivatives, such as antihypertensive, anti-inflammatory, antischizophrenia, antibacterial, anti-HIV, hypnotics, antiallergic, analgesic, fibrinogen receptor antagonist, bacterial DNA gyrase B inhibitor and antitumor activities. [10][11][12][13][14][15][16][17][18][19][20][21][22] Also they have wide range of applications in organic functional materials such as fluorescent dyes 23 and liquid crystals.…”