N-[3-(dimethylamino)propyl]-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide | 55387-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: N-[3-(dimethylamino)propyl]-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
• 英文别名: N-[3-(dimethylamino)propyl]-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide；propoxicam；proxicam；N-[3-(dimethylamino)propyl]-[4-hydroxy-2-methyl-1,1-dioxo-2H-1,2-benzo-thiazin-3-yl]carboxamide；N-[3-(dimethylamino)propyl]-4-hydroxy-2-methyl-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
• CAS: 55387-73-0
• 化学式: C₁₅H₂₁N₃O₄S
• 分子量: 339.415
• InChiKey: FSUMGRQFCMFLKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  98.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[3-(dimethylamino)propyl]-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide 、 碘甲烷 反应 24.0h， 生成 [3-(2-methyl-1,1-dioxo-2H-1,2-benzothiazin-3-yl)carbonylamino]propyltrimethylammonium iodide
  参考文献：
  名称：

  Quaternary ammonium compounds

  摘要：

  具有与化学式（Ia）或（Ib）相对应的化合物： 其中： M代表可用于治疗或诊断由对软骨的攻击引起的病理的分子， R1、R2和R3代表烷基基团，或R1、R2和R3与携带它们的氮原子一起形成杂环， X代表（C1-C6）烷基链，其中一个或多个—CH2—基团可以选择性地被硫原子、氧原子或—NR—、—CO—、—CO—NH—、—CO2—、—SO—或—SO2—基团所取代， n代表0或1， Hal代表卤素原子， 或， R4代表烷基基团， Hal代表卤素原子， 代表可用于治疗或诊断由对软骨的攻击引起的病理的分子，其中氮原子可以选择性地包含在饱和或不饱和的含氮杂环系统中，或包含在双键中；以及其药物组成物。

  公开号：

  US06759406B1
• 作为产物：
  描述：

  2,3-二氢-3-氧代-1,2-苯并异噻唑-2-乙酸甲酯1,1-二氧化物 在 sodium methylate 作用下， 以 二甲基亚砜 、 xylene 为溶剂， 反应 24.0h， 生成 N-[3-(dimethylamino)propyl]-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
  参考文献：
  名称：

  New Quaternary Ammonium Oxicam Derivatives Targeted toward Cartilage:  Synthesis, Pharmacokinetic Studies, and Antiinflammatory Potency

  摘要：

  Analogues of nonsteroidal antiinflammatory drugs (NSAIDs) oxicams, in which the active group was linked to a quaternary ammonium function [(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide-3-carboxamido)2-methylpyridinium iodide or piroxicam-N+ and [3-(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide-3-carboxamido)propyl]trimethylammonium iodide or propoxicam-N+] were synthesized. Compounds were labeled with tritium for piroxicam-N+ and carbon-14 for propoxicam-N+. Pharmacokinetic studies conducted on rats showed that these molecules were able to highly concentrate in joint cartilages but their bioavailability by the oral way was low. Only propoxicam-N+ exhibited a sufficient water solubility to be administered intravenously. This molecule was able to restore proteoglycans biosynthesis in cultured articular chondrocytes treated with Interleukin-1 beta with an efficiency identical to that of indomethacin. These results suggest that the functionalization of oxicam derivatives by a quaternary ammonium group greatly increases their affinity toward articular cartilage without eliminating their pharmacological activity. New drugs synthesized according to this scheme could be useful to obtain a significant decrease of the efficient administered dose and consequently an attenuation of adverse effects such as digestive toxicity.

  DOI：

  10.1021/jm991120o

文献信息

• New quaternary ammonium oxicam derivatives: synthesis and in vitro antiosteoarthritis evaluation
  作者：Aurélien Vidal、Jean-Michel Chezal、Emmanuelle Mounetou

  DOI：10.1016/j.ejmech.2009.09.026

  日期：2010.1

  A series of new oxicam derivatives bearing a quaternary ammonium (QA) moiety was synthesized and evaluated in vitro for antiosteoarthritis properties. Propyltrimethyl ammonium 3 and propyldie-thylmethyl ammonium 11 stimulated aggrecan expression and mitigated the inhibitory action of IL-1. QA derivative 3 also increased TGF-beta 2 and type II receptor expression. These results suggest that such derivatives may not only inhibit the osteoarthritis degradation process but also stimulate its regeneration. QA derivatives 3 and 11 offer potential for developing new therapeutic approaches to osteoarthritis treatment. (C) 2009 Elsevier Masson SAS. All rights reserved.