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环氧化酶与5-脂氧合酶双重抑制剂3-羟基-5-三氟甲基-N-(2-(2-噻吩基)-2-苯基乙烯基)-苯并(b)噻吩-2-甲酰胺的药理学

Pharmacology of the dual inhibitor of cyclooxygenase and 5-lipoxygenase 3-hydroxy-5-trifluoromethyl-N-(2-(2-thienyl)-2-phenyl-ethenyl)-benzo (b)thiophene-2-carboxamide.

作者信息

Bailey P J, Dallob A L, Allison D L, Anderson R L, Bach T, Durette P L, Hand K M, Hopple S L, Luell S, Meurer R

机构信息

Department of Biochemistry/Molecular Biology, Merck Sharp & Dohme Research Laboratories, Rahway, NJ.

出版信息

Arzneimittelforschung. 1988 Mar;38(3):372-8.

PMID:3132928
Abstract

3-Hydroxy-5-trifluoromethyl-N-(2-(2-thienyl)-2-phenyl-ethenyl)- benzo (b) thiophene-2-carboxamide (L-652,343) is an inhibitor of cyclooxygenase and 5-lipoxygenase in vitro and inhibits the synthesis of the products of both these pathways in whole cells. L-652,343 is an inhibitor of the acute edema induced by carrageenan in vivo and is active topically in suppressing arachidonic acid induced inflammation in the skin. The compound is an effective inhibitor of the chronic inflammation of adjuvant and type II collagen induced polyarthritis. L-652,343 is an extremely potent analgesic in models of yeast and platelet activating factor induced hyperalgesia in rats and phenylbenzoquinone-induced writhing in mice. The fever induced by Brewer's yeast is lowered by L-652,343. The ulcerogenicity and gastric bleeding induced by L-652,343 is extremely low, providing a favorable therapeutic index which is superior to that of indomethacin, piroxicam and phenylbutazone.

摘要

3-羟基-5-三氟甲基-N-(2-(2-噻吩基)-2-苯基乙烯基)-苯并(b)噻吩-2-甲酰胺(L-652,343)在体外是环氧化酶和5-脂氧合酶的抑制剂,并且在全细胞中抑制这两条途径的产物合成。L-652,343在体内是角叉菜胶诱导的急性水肿的抑制剂,并且在局部抑制花生四烯酸诱导的皮肤炎症方面具有活性。该化合物是佐剂和II型胶原诱导的多关节炎慢性炎症的有效抑制剂。L-652,343在大鼠酵母和血小板活化因子诱导的痛觉过敏模型以及小鼠苯醌诱导的扭体模型中是一种极其有效的镇痛药。L-652,343可降低啤酒酵母诱导的发热。L-652,343诱导的溃疡形成和胃出血极低,提供了优于吲哚美辛、吡罗昔康和保泰松的良好治疗指数。

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