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.
• Quaternary ammonium compounds
  申请人：Les Laboratoires Servier

  公开号：US06759406B1

  公开（公告）日：2004-07-06

  Compounds of formula corresponding to either formula (Ia) or (Ib): wherein: M represents a molecule that can be used for the treatment or diagnosis of pathologies caused by attack on the cartilage, R1, R2 and R3 represent an alkyl group, or R1, R2 and R3, together with the nitrogen atom carrying them, form a heterocycle, X represents a (C1-C6)alkylene chain in which one or more —CH2— groups are optionally replaced by a sulphur atom, an oxygen atom, or an —NR—, —CO—, —CO—NH—, —CO2—, —SO— or —SO2— group, n represents 0 or 1, Hal represents a halogen atom, or, R4 represents an alkyl group, Hal represents a halogen atom, represents a molecule that can be used for the treatment or diagnosis of pathologies caused by attack on the cartilage, wherein the nitrogen atom may optionally be included in a saturated or unsaturated nitrogen-containing heterocyclic system, or included in a double bond; and pharmaceutical compositions thereof.

  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。
• New Quaternary Ammonium Oxicam Derivatives Targeted toward Cartilage:  Synthesis, Pharmacokinetic Studies, and Antiinflammatory Potency
  作者：Colette Nicolas、Michel Verny、Isabelle Giraud、Monique Ollier、Maryse Rapp、Jean-Claude Maurizis、Jean-Claude Madelmont

  DOI：10.1021/jm991120o

  日期：1999.12.1

  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.