meloxicam benzoic acid | 1174325-83-7

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: meloxicam benzoic acid
• 英文别名: benzoic acid;4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1lambda6,2-benzothiazine-3-carboxamide；benzoic acid;4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
• CAS: 1174325-83-7
• 化学式: C₇H₆O₂*C₁₄H₁₃N₃O₄S₂
• 分子量: 473.53
• InChiKey: OTUFQDOILUEYPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.34
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  174
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  美洛昔康 、 苯甲酸 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 meloxicam benzoic acid
  参考文献：
  名称：

  美洛昔康与苯甲酸共晶的合成及晶体结构

  摘要：

  美洛昔康 [4-羟基-2-甲基-N-(5-甲基-1,3-噻唑-2-基)-1,1-二氧代-2H-1λ6,2 1:1 共晶的单晶-苯并噻嗪-3-甲酰胺]，MXM，与苯甲酸，BZA，从 THF 溶液中结晶。使用具有不同极性的流体添加剂溶剂：苯、甲苯、邻二甲苯、间二甲苯、对二甲苯、四氢呋喃和水。后者特别环保，可以成为工业生产的理想选择。比较了剑桥数据库最新版本中存放的所有 MXM 共晶的晶体结构，以便将这些结构中的非共价相互作用与 Cysewski 进行的溶解度理论分析得出的结论相关联（J . Mol. 模型 24:112, 2018)。

  DOI：

  10.1007/s11224-018-1166-5

文献信息

• In vivo studies of crystalline forms of meloxicam
  申请人：Hanna Mazen

  公开号：US20090203680A1

  公开（公告）日：2009-08-13

  The invention is directed to novel crystalline forms of meloxicam. These novel crystalline forms of meloxicam have improved bioavailability, an enhanced rate of dissolution and shorter time to C max in blood, as compared to pure meloxicam.

  本发明涉及美洛昔康的新晶体形式。这些新晶体形式的美洛昔康具有比纯美洛昔康更好的生物利用度，更快的溶解速度和更短的达到血浆Cmax的时间。
• Preparation and studies of the co-crystals of meloxicam with carboxylic acids
  作者：S. A. Myz、T. P. Shakhtshneider、N. A. Tumanov、E. V. Boldyreva

  DOI：10.1007/s11172-012-0248-6

  日期：2012.9

  Mechanical treatment with addition of some liquid, crystallization from solutions, and heating of the mixture components preliminary subjected to mechanical treatment were the methods used for the preparation of the co-crystals of 4-hydroxy-2-methyl-N-(5-methylthiazol-2-yl)-2H-1,2-benzothiazin-3-carboxamide 1,1-dioxide (meloxicam) with carboxylic acids. It was shown that preliminary mechanical treatment plays significant role for the synthesis, whereas the addition of small amounts of solvents accelerates the process. The co-crystals were obtained for 17 mixtures of meloxicam—carboxylic acid. The use of the co-crystals of meloxicam in the compositions of improved pharmaceutical forms was found promising, which was attributable to the fact that the dissolution rate and the solubility of the co-crystals of meloxicam with the carboxylic acids under study are higher than those for meloxicam itself.

  在制备 4-羟基-2-甲基-N-(5-甲基噻唑-2-基)-2H-1,2-苯并噻嗪-3-甲酰胺 1,1-二氧化物（美洛昔康）与羧酸的共晶体时，采用了添加一些液体的机械处理法、从溶液中结晶法和加热初步经过机械处理的混合物组分法。研究表明，初步机械处理对合成起着重要作用，而添加少量溶剂则可加速合成过程。17 种美洛昔康与羧酸的混合物都获得了共晶体。研究发现，美洛昔康与羧酸的共晶体的溶解速率和溶解度均高于美洛昔康本身，因此在改良药剂配方中使用美洛昔康共晶体大有可为。
• Supramolecular Architectures of Meloxicam Carboxylic Acid Cocrystals, a Crystal Engineering Case Study
  作者：Miranda L. Cheney、David R. Weyna、Ning Shan、Mazen Hanna、Lukasz Wojtas、Michael J. Zaworotko

  DOI：10.1021/cg100514g

  日期：2010.10.6

  Meloxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility and high permeability prescribed for indications of arthritis, primary dysmenorrhea, fever, and pain, in this contribution, we apply crystal engineering and the supramolecular synthon approach to prepare novel meloxicam cocrystal forms with various pharmaceutically acceptable or toxicologically qualified carboxylic acids. As a result, 19 pharmaceutical cocrystals including one cocrystal of a salt are synthesized by solid-state and solution methods. All resulting cocrystals are characterized by X-ray diffraction. infrared. and thermal analyses. In particular, crystal structures of six rneloxicam cocrystals are determined and reported, namely. meloxicam . 1-hydroxy-2-naphthoic acid cocrystal (1), meloxicam . glutaric acid cocrystal (2), meloxicam . L-malic acid cocrystal lit salt (3), meloxicam . salicylic acid cocrystal form 111 (4), meloxicam . fumaric acid cocrystal (5), and meloxicam . succinic acid cocrystal (6). The supramolecular assembly of each cocrystal is analyzed and discussed. It is observed that the meloxicam dimer is robust since this motif is observed in five out of six meloxicam cocrystal structures that have been determined. As part of the continuous development, the resulting meloxicam cocrystal forms will be further investigated to explore improved physicochemical and pharmacological properties.
• IN VIVO STUDIES OF CRYSTALLINE FORMS OF MELOXICAM
  申请人：Thar Pharmaceuticals Inc.

  公开号：EP2244712B1

  公开（公告）日：2015-08-05
• In Vivo Studies of Crystalline Forms of Meloxicam
  申请人：Hanna Mazen

  公开号：US20120149692A1

  公开（公告）日：2012-06-14

  The invention is directed to novel crystalline forms of meloxicam. These novel crystalline forms of meloxicam have improved bioavailability, an enhanced rate of dissolution and shorter time to C max in blood, as compared to pure meloxicam.