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酮咯酸

酮咯酸

CAS号:74103-06-3
英文名:Ketorolac
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化合物简介
Ketorolac or ketorolac tromethamine is a non-steroidal anti-inflammatory drug (NSAID) in the family of heterocyclic acetic acid derivatives, used as an analgesic. Ketorolac was developed in 1989 by Syntex Corp. (now Roche Bioscience, which is a wholly owned subsidiary of Roche holding Ltd., the parent company of Roche). It was approved by FDA on 30 November 1989 and introduced as Toradol by Syntex. The ophthalmic (i.e., eye-drop) form was approved by FDA on 9 November 1992 and was introduced as Acular eye drops by Allergan under license from Syntex. An intranasal formulation of ketorolac tromethamine was approved by FDA on 14 May 2010 and introduced as Sprix Nasal Spray by Daiichi Sankyo for short-term management of moderate to moderately severe pain requiring analgesia at the opioid level.
基本信息
编号系统
物化性质
安全信息
生产方法及用途
生产方法
方法1:吡咯和二甲硫醚在N-氯代丁二酰亚胺作用下,得到2-(甲硫基)吡咯。2-(甲硫基)吡咯在含三氯氧磷的二氯乙烷溶液中,在回流下用苯甲酰二甲胺进行酰化,得到2-(甲硫基)-5-苯甲酰基毗咯。该化合物和螺二氧杂辛烷二酮缩合得化合物(I)。化合物(I)先氧化,然后甲醇解,得二酯化物(Ⅱ)。(Ⅱ)在二甲基甲酰胺中,氢化钠作用下环合得到化合物(Ⅲ)。(Ⅲ)水解并脱羧得到酮咯酸。
方法2:氨基乙醇和3-氧戊二酸二甲酯反应,得到化合物(Ⅳ)。(Ⅳ)和溴乙醛加热环合,得化合物(V)。(V)甲磺酰化后,再碘代得到化合物(Ⅵ)。(Ⅵ)在碱的作用下环合得化合物(Ⅶ)。(Ⅶ)水解后,再重新单酯化、脱羧,得化合物(Ⅷ)。(Ⅷ)用苯甲酰二甲胺酰化,接着水解得酮咯酸。
方法3:吡咯在三氯氧磷作用下,和N-苯甲酰基吗啉在二氯乙烷中反应,得2-苯甲酰基吡咯,收率72.3%。高锰酸钾、二乙酸锰四水合物及冰乙酸一起温热,再小心滴入乙酸酐。滴毕,冷至室温,加入原甲酸三乙酯、2-苯甲酰基吡咯和无水乙酸钠,在65℃下充入氮气搅拌。处理后得原甲酸三乙酯衍生物,收率86%。该衍生物在碳酸钾和溴化四正丁基铵作用下,在二氯乙烷中回流,得到环合产物;不用提纯,水解、酸化后得酮咯酸,收率66.7%。
用途
1.消炎镇痛药,并有抗血小板凝集作用。
2.本品为强效镇痛、中度抗炎作用的非甾体抗炎药.该药镇痛作用同吗啡相当,强于阿司匹林、吲哚美辛及萘普生.与阿片类镇痛药相比,其优点是起效快、无成瘾性、无呼吸抑制作用.临床用于抗炎镇痛,也用于白内障手术后止痛及眼部抗炎.本品具有抗血小板凝集作用.