4-羟基-N-[5-(羟基甲基)-1,3-噻唑-2-基]-2-甲基-2H-1,2-苯并噻嗪-3-甲酰胺1,1-二氧化物 | 130262-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 中文名称: 4-羟基-N-[5-(羟基甲基)-1,3-噻唑-2-基]-2-甲基-2H-1,2-苯并噻嗪-3-甲酰胺1,1-二氧化物
• 中文别名: 5'-羟基美洛昔康
• 英文名称: 5'-Hydroxy-Meloxicam
• 英文别名: 5′-hydroxymethyl 5′-desmethyl meloxicam；5'-hydroxymethylmeloxicam；5-hydroxymethyl-meloxicam；5′-hydroxy meloxicam；5-Hydroxymethyl meloxicam；4-hydroxy-N-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-2-methyl-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
• CAS: 130262-92-9
• 化学式: C₁₄H₁₃N₃O₅S₂
• 分子量: 367.406
• InChiKey: LOOSAJMIEADILV-UHFFFAOYSA-N

物化性质

• 熔点：
  230-232°C
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  156
• 氢给体数：
  3
• 氢受体数：
  8

ADMET

代谢

5-羟基甲基美洛昔康是美洛昔康在人身体内已知的一种代谢物。

5-Hydroxymethyl meloxicam is a known human metabolite of meloxicam.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  美洛昔康 在 quinine 3-monooxygenase 、 还原型辅酶II(NADPH)四钠盐 、 奎尼丁 作用下， 以 二甲基亚砜 为溶剂， 生成 4-羟基-N-[5-(羟基甲基)-1,3-噻唑-2-基]-2-甲基-2H-1,2-苯并噻嗪-3-甲酰胺1,1-二氧化物
  参考文献：
  名称：

  Ludwig, Eva; Schmid, Jochen; Beschke, Klaus, Journal of Pharmacology and Experimental Therapeutics, 1999, vol. 290, # 1, p. 1 - 8

  摘要：

  DOI：

文献信息

• A mass spectrometric study on meloxicam metabolism in horses and the fungus<i>Cunninghamella elegans,</i>and the relevance of this microbial system as a model of drug metabolism in the horse
  作者：Annica Tevell Åberg、Charlotte Olsson、Ulf Bondesson、Mikael Hedeland

  DOI：10.1002/jms.1575

  日期：2009.7

  This paper describes a study where the metabolism of the non-steroidal anti-inflammatory drug meloxicam was investigated in six horses and in the filamentous fungus Cunninghamella elegans. The metabolites identified were compared between the species, and then the fungus was used to produce larger amounts of the metabolites for future use as reference material. C. elegans proved to be a good model of phase I meloxicam metabolism in horses since all four metabolites found were the same in both species. Apart from the two main metabolites, 5′-hydroxymethylmeloxicam and 5′-carboxymeloxicam, a second isomer of hydroxymeloxicam and dihydroxylated meloxicam were detected for the first time in horse urine and the microbial incubations. Phase II metabolites were not discovered in the C. elegans samples but hydroxymeloxicam glucuronide was detected intact in horse urine for the first time in this study. Urine from six horses was further analyzed in a semi-quantitative sense and 5′-hydroxymethylmeloxicam gave peaks with much higher intensity compared to the parent drug and the other metabolites, and was detected for at least 14 days after the last given dose in some of the horses. From the results presented in this article, we suggest that analytical methods developed for the detection of meloxicam in horse urine after prohibited use should focus on the 5′-hydroxymethyl metabolite and that C. elegans can be used to produce large amounts of this metabolite for potential future use as a reference compound. Copyright © 2009 John Wiley & Sons, Ltd.

  本文介绍了一项研究，该研究调查了非甾体类消炎药美洛昔康在六匹马和丝状真菌库宁汉菌（Cunninghamella elegans）中的代谢情况。研究人员比较了不同物种之间已鉴定出的代谢物，然后利用真菌生产出更大量的代谢物，作为今后的参考材料。事实证明，秀丽隐杆线虫是马体内美洛昔康第一阶段代谢的良好模型，因为在这两个物种中发现的所有四种代谢物都是相同的。除了 5′-羟甲基美洛昔康和 5′-羧基美洛昔康这两种主要代谢物外，还首次在马尿和微生物培养液中检测到羟基美洛昔康的第二异构体和二羟基美洛昔康。在马尿样本中没有发现第二阶段代谢物，但在本研究中首次在马尿中完整地检测到羟甲昔康葡萄糖醛酸苷。对六匹马的尿液进行了进一步的半定量分析，与母药和其他代谢物相比，5′-羟甲基美洛昔康的峰值强度要高得多，而且在一些马的尿液中，在最后一次给药后的至少 14 天内都能检测到这种代谢物。根据本文介绍的结果，我们建议为检测马尿中禁用药物后的美洛昔康而开发的分析方法应侧重于 5′-羟甲基代谢物，并可利用秀丽隐杆线虫生产大量这种代谢物，以便将来用作参考化合物。Copyright © 2009 John Wiley & Sons, Ltd. 版权所有。
• Ludwig, Eva; Schmid, Jochen; Beschke, Klaus, Journal of Pharmacology and Experimental Therapeutics, 1999, vol. 290, # 1, p. 1 - 8
  作者：Ludwig, Eva、Schmid, Jochen、Beschke, Klaus、Ebner, Thomas

  DOI：——

  日期：——