2-{[[(2,3-dimethylphenyl)amino]benzoyl]amino}ethanesulfonic acid | 1191073-68-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-{[[(2,3-dimethylphenyl)amino]benzoyl]amino}ethanesulfonic acid
• 英文别名: 2-[[2-(2,3-Dimethylanilino)benzoyl]amino]ethanesulfonic acid
• CAS: 1191073-68-3
• 化学式: C₁₇H₂₀N₂O₄S
• 分子量: 348.423
• InChiKey: NSLUAQWHUVJEGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  扑湿痛 在 氯甲酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 aq. phosphate buffer 、 水 为溶剂， 反应 3.5h， 生成 2-{[[(2,3-dimethylphenyl)amino]benzoyl]amino}ethanesulfonic acid
  参考文献：
  名称：

  The Nonenzymatic Reactivity of the Acyl-Linked Metabolites of Mefenamic Acid toward Amino and Thiol Functional Group Bionucleophiles

  摘要：

  甲灭酸 (MFA) 是一种含羧酸的非甾体抗炎药物，在代谢过程中会生成具有化学反应的 MFA-1- O -酰基葡萄糖醛酸苷 (MFA-1- O -G)、MFA-酰基腺苷酸 (MFA-AMP) 和 MFA- S -酰基辅酶 A (MFA-CoA)，它们都具有亲电性，能够酰化生物大分子上的亲核位点。在本研究中，我们研究了每种 MFA 乙酰连接代谢物在受体生物大分子 Gly、Tau、l-谷胱甘肽（GSH）和 N-乙酰半胱氨酸（NAC）上酰化氨基和硫醇官能团的非酶能力。在生理条件下，在缓冲液中将每种 MFA 乙酰连接代谢物（1 μ M）与 Gly、Tau、GSH 或 NAC（10 mM）进行体外培养，结果表明 MFA-CoA 对 GSH 和 NAC 的半胱氨酸-巯基酰化的反应活性分别是 MFA-AMP 的 11.5 倍和 19.5 倍。然而，MFA-AMP 对甘氨酸和 Tau 的反应活性更高，对牛磺酸 N-酰基酰胺化的反应活性是其相应 CoA 硫代酯的 17.5 倍，而 MFA-CoA 对甘氨酸的反应活性很小。此外，甲灭酸-S-酰基谷胱甘肽（MFA-GSH）对 NAC 的反应活性分别是 MFA-CoA 和 MFA-AMP 的 5.6 倍和 108 倍。与 MFA-AMP 和 MFA-CoA 相比，MFA-1- O -G 对所有四种亲核物的反应性都不明显。在大鼠体外肝细胞 MFA（100 μ M）培养液中也检测到了 MFA-AMP、MFA-CoA、MFA-1- O -G、MFA-GSH 和甲灭酸-牛磺酸，而甲灭酸-甘氨酸没有检测到。这些结果表明，MFA-AMP 会选择性地与甘氨酸和赖氨酸的氨基官能团发生非酶反应，MFA-CoA 会选择性地与 GSH 和 NAC 的硫醇官能团发生非酶反应，而 MFA-GSH 会与 GSH 的硫醇官能团发生非酶反应，所有这些反应都有可能在体内引发特异性毒性。

  DOI：

  10.1124/dmd.113.053223

文献信息

• NOVEL COMPOUNDS DERIVED FROM TAURINE, PROCESS OF THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE
  申请人：Vizioli Ednir de Oliveira

  公开号：US20110118303A1

  公开（公告）日：2011-05-19

  The present invention relates to compounds derived from taurine with non-steroidal anti inflammatory activity. In a first embodiment, the present invention relates to compounds derived from taurine, in which taurine is bound directly by means of an amide bond or through an spacing group, to a compound selected from the group of non-steroidal anti inflammatory compounds, cited as derived from taurine presenting the Formula (I): in which R means the component with non-steroidal anti inflammatory activity. In a second embodiment, the invention provides a process for obtaining the compounds of Formula (I) by reaction of taurine with a compound belonging to the group of non-steroidal anti inflammatory (NSAIs), in order to obtain a compound derived from taurine by direct bond or through a spacing group of the taurine to the NSAI. The invention also relates to the pharmaceutical compositions comprising at least one compound derived from taurine presenting non-steroidal anti inflammatory activity.
• US8569335B2
  申请人：——

  公开号：US8569335B2

  公开（公告）日：2013-10-29
• [EN] NOVEL COMPOUNDS DERIVED FROM TAURINE, PROCESS OF THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE<br/>[FR] NOUVEAUX COMPOSÉS DÉRIVÉS DE TAURINE, PROCESSUS DE PRÉPARATION DE CES COMPOSÉS ET COMPOSITION PHARMACEUTIQUE LES CONTENANT
  申请人：EMS SA

  公开号：WO2009124371A2

  公开（公告）日：2009-10-15

  The present invention relates to compounds derived from taurine with non-steroidal anti inflammatory activity. In a first embodiment, the present invention relates to compounds derived from taurine, in which taurine is bound directly by means of an amide bond or through an spacing group, to a compound selected from the group of non-steroidal anti inflammatory compounds, cited as derived from taurine presenting the Formula (I): in which R means the component with non-steroidal anti inflammatory activity. In a second embodiment, the invention provides a process for obtaining the compounds of Formula (I) by reaction of taurine with a compound belonging to the group of non-steroidal anti inflammatory (NSAIs), in order to obtain a compound derived from taurine by direct bond or through a spacing group of the taurine to the NSAI. The invention also relates to the pharmaceutical compositions comprising at least one compound derived from taurine presenting non-steroidal anti inflammatory activity.
• The Nonenzymatic Reactivity of the Acyl-Linked Metabolites of Mefenamic Acid toward Amino and Thiol Functional Group Bionucleophiles
  作者：Howard Horng、Leslie Z. Benet

  DOI：10.1124/dmd.113.053223

  日期：2013.11

  Mefenamic acid (MFA), a carboxylic acid–containing nonsteroidal anti-inflammatory drug, is metabolized into the chemically-reactive MFA-1- O -acyl-glucuronide (MFA-1- O -G), MFA-acyl-adenylate (MFA-AMP), and the MFA- S -acyl-coenzyme A (MFA-CoA), all of which are electrophilic and capable of acylating nucleophilic sites on biomolecules. In this study, we investigate the nonenzymatic ability of each MFA acyl-linked metabolite to transacylate amino and thiol functional groups on the acceptor biomolecules Gly, Tau, l-glutathione (GSH), and N -acetylcysteine (NAC). In vitro incubations with each of the MFA acyl-linked metabolites (1 μ M) in buffer under physiologic conditions with Gly, Tau, GSH, or NAC (10 mM) revealed that MFA-CoA was 11.5- and 19.5-fold more reactive than MFA-AMP toward the acylation of cysteine-sulfhydryl groups of GSH and NAC, respectively. However, MFA-AMP was more reactive toward both Gly and Tau, 17.5-fold more reactive toward the N -acyl-amidation of taurine than its corresponding CoA thioester, while MFA-CoA displayed little reactivity toward glycine. Additionally, mefenamic acid- S -acyl-glutathione (MFA-GSH) was 5.6- and 108-fold more reactive toward NAC than MFA-CoA and MFA-AMP, respectively. In comparison with MFA-AMP and MFA-CoA, MFA-1- O -G was not significantly reactive toward all four bionucleophiles. MFA-AMP, MFA-CoA, MFA-1- O -G, MFA-GSH, and mefenamic acid-taurine were also detected in rat in vitro hepatocyte MFA (100 μ M) incubations, while mefenamic acid-glycine was not. These results demonstrate that MFA-AMP selectively reacts with the amino functional groups of glycine and lysine nonenzymatically, MFA-CoA selectively reacts nonenzymatically with the thiol functional groups of GSH and NAC, and MFA-GSH reacts with the thiol functional group of GSH nonenzymatically, all of which may potentially elicit an idiosyncratic toxicity in vivo.

  甲灭酸 (MFA) 是一种含羧酸的非甾体抗炎药物，在代谢过程中会生成具有化学反应的 MFA-1- O -酰基葡萄糖醛酸苷 (MFA-1- O -G)、MFA-酰基腺苷酸 (MFA-AMP) 和 MFA- S -酰基辅酶 A (MFA-CoA)，它们都具有亲电性，能够酰化生物大分子上的亲核位点。在本研究中，我们研究了每种 MFA 乙酰连接代谢物在受体生物大分子 Gly、Tau、l-谷胱甘肽（GSH）和 N-乙酰半胱氨酸（NAC）上酰化氨基和硫醇官能团的非酶能力。在生理条件下，在缓冲液中将每种 MFA 乙酰连接代谢物（1 μ M）与 Gly、Tau、GSH 或 NAC（10 mM）进行体外培养，结果表明 MFA-CoA 对 GSH 和 NAC 的半胱氨酸-巯基酰化的反应活性分别是 MFA-AMP 的 11.5 倍和 19.5 倍。然而，MFA-AMP 对甘氨酸和 Tau 的反应活性更高，对牛磺酸 N-酰基酰胺化的反应活性是其相应 CoA 硫代酯的 17.5 倍，而 MFA-CoA 对甘氨酸的反应活性很小。此外，甲灭酸-S-酰基谷胱甘肽（MFA-GSH）对 NAC 的反应活性分别是 MFA-CoA 和 MFA-AMP 的 5.6 倍和 108 倍。与 MFA-AMP 和 MFA-CoA 相比，MFA-1- O -G 对所有四种亲核物的反应性都不明显。在大鼠体外肝细胞 MFA（100 μ M）培养液中也检测到了 MFA-AMP、MFA-CoA、MFA-1- O -G、MFA-GSH 和甲灭酸-牛磺酸，而甲灭酸-甘氨酸没有检测到。这些结果表明，MFA-AMP 会选择性地与甘氨酸和赖氨酸的氨基官能团发生非酶反应，MFA-CoA 会选择性地与 GSH 和 NAC 的硫醇官能团发生非酶反应，而 MFA-GSH 会与 GSH 的硫醇官能团发生非酶反应，所有这些反应都有可能在体内引发特异性毒性。