5325-18-8Relevant academic research and scientific papers
Design of novel potent antihyperlipidemic agents with antioxidant/anti- inflammatory properties: Exploiting phenothiazine's strong antioxidant activity
Matralis, Alexios N.,Kourounakis, Angeliki P.
, p. 2568 - 2581 (2014/04/17)
Because atherosclerosis is an inflammatory process involving a series of pathological events such as dyslipidemia, oxidative stress, and blood clotting mechanisms, we hereby report the synthesis and evaluation of novel compounds in which antioxidant, anti-inflammatory, and squalene synthase (SQS) inhibitory/hypolipidemic activities are combined in simple molecules through design. The coupling of two different pharmacophores afforded compounds 1-12, whose biological profile was markedly improved compared to those of parent lead structures (i.e., the hypolipidemic 2-hydroxy-2-aryl-(benzo)oxa(or thia)zine and the antioxidant phenothiazine). Most derivatives strongly inhibited in vitro microsomal lipid and LDL peroxidation, exhibiting potent free-radical scavenging activity. They further significantly inhibited SQS activity and showed remarkable antidyslipidemic activity in vivo in animal models of acute and high-fat-induced hyperlipidemia. Finally, several compounds showed anti-inflammatory activity in vitro, inhibiting cycloxygenase (COX-1/2) activity. The multimodal properties of the new compounds and especially their combined antioxidant/SQS/COX inhibitory activity render them interesting lead compounds for further evaluation against atherosclerosis.
N-(4-Substituted-thiazolyl)oxamic Acid Derivatives, a New Series of Potent, Orally Actve Antiallergy Agents
Hargrave, Karl D.,Hess, Friedrich K.,Oliver, James T.
, p. 1158 - 1163 (2007/10/02)
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 oxamic acid ethanolamine salt (61, PRH-836-EA), has been selected for further pharmacological evaluation.
