[4-(methanesulfonylamino-methyl)-phenyl]-acetic acid methyl ester | 808753-03-9

• 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: [4-(methanesulfonylamino-methyl)-phenyl]-acetic acid methyl ester
• 英文别名: methyl 2-[4-(methanesulfonamidomethyl)phenyl]acetate
• CAS: 808753-03-9
• 化学式: C₁₁H₁₅NO₄S
• 分子量: 257.31
• InChiKey: KUTSCHHNOJJGPP-UHFFFAOYSA-N

物化性质

• 沸点：
  397.5±44.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-(methanesulfonylamino-methyl)-phenyl]-acetic acid methyl ester 在 lithium hydroxide 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 N-[(S)-2-((S)-3-Hydroxy-pyrrolidin-1-yl)-1-phenyl-ethyl]-2-[4-(methanesulfonylamino-methyl)-phenyl]-N-methyl-acetamide
  参考文献：
  名称：

  Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity

  摘要：

  Some K opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 mu M) while displaying high affinity toward the cloned human K opioid receptor, good kappa/delta and kappa/mu selectivity, and potent in vitro and in vivo agonist activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.020
• 作为产物：
  描述：

  4-溴苯乙酸甲酯 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、482.63 kPa 条件下， 生成 [4-(methanesulfonylamino-methyl)-phenyl]-acetic acid methyl ester
  参考文献：
  名称：

  Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity

  摘要：

  Some K opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 mu M) while displaying high affinity toward the cloned human K opioid receptor, good kappa/delta and kappa/mu selectivity, and potent in vitro and in vivo agonist activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.020

文献信息

• Sulfonylamino phenylacetamide derivatives and methods of their use
  申请人：——

  公开号：US20040254156A1

  公开（公告）日：2004-12-16

  Sulfonylamino phenylacetamide derivatives of the general formula 1 are disclosed. Pharmaceutical compositions containing the compounds and methods for their use are also disclosed. In certain embodiments, the compounds of the invention that, preferably: (1) bind with high affinity to &kgr; opioid receptors; (2) display good opioid receptor selectivity of &kgr; versus &mgr; and &kgr; versus &dgr;; and (3) do not substantially inhibit cytochrome P450 enzymatic activity, in particular CYP2D6, CYP2C9 and CYP3A4.

  揭示了通式1的磺酰氨基苯乙酰胺衍生物。还公开了含有这些化合物的药物组合物和它们的使用方法。在某些实施例中，本发明的化合物最好具有以下特征：(1) 与κ阿片受体结合的亲和力高；(2) 在κ与μ受体以及κ与δ受体之间显示良好的阿片受体选择性；以及(3) 不显著抑制细胞色素P450酶的活性，特别是CYP2D6、CYP2C9和CYP3A4。
• US6992193B2
  申请人：——

  公开号：US6992193B2

  公开（公告）日：2006-01-31
• [EN] SULFONYLAMINO PHENYLACETAMIDE DERIVATIVES AND METHODS OF THEIR USE<br/>[FR] DERIVES DE SULFONYLAMINO PHENYLACETAMIDE ET LEURS PROCEDES D'UTILISATION
  申请人：ADOLOR CORP

  公开号：WO2005004796A2

  公开（公告）日：2005-01-20

  [EN] Sulfonylamino phenylacetamide derivatives of the general formula (I) are disclosed. Pharmaceutical compositions containing the compounds and methods for their use are also disclosed. In certain embodiments, the compounds of the invention that, preferably: (1) bind with high affinity to kappa opioid receptors; (2) display good opioid receptor selectivity of kappa versus µ and kappa versus delta; and (3) do not substantially inhibit cytochrome P450 enzymatic activity, in particular CYP2D6, CYP2C9 and CYP3A4.
  [FR] La présente invention a trait à des dérivés de sulfonylamino phénylacétamide de formule générale (I). L'invention a également trait à des compositions pharmaceutiques contenant les composés et leurs procédés d'utilisation. Dans certains modes de réalisation, les composés de l'invention, de préférence : (1) se lient avec une grande affinité aux récepteurs opioïdes kappa ; (2) présentent une bonne sélectivité de récepteurs opioïdes kappa par rapport aux opioïdes mu et par rapport aux opioïdes delta ; et (3) ne présentent pas une inhibition sensible de l'activité enzymatique de cytochrome P450, notamment le CYP2D6, le CYP2C9 et le CYP3A4.
• Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity
  作者：Bertrand Le Bourdonnec、Christopher W. Ajello、Pamela R. Seida、Roberta G. Susnow、Joel A. Cassel、Serge Belanger、Gabriel J. Stabley、Robert N. DeHaven、Diane L. DeHaven-Hudkins、Roland E. Dolle

  DOI：10.1016/j.bmcl.2005.03.020

  日期：2005.5

  Some K opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 mu M) while displaying high affinity toward the cloned human K opioid receptor, good kappa/delta and kappa/mu selectivity, and potent in vitro and in vivo agonist activity. (c) 2005 Elsevier Ltd. All rights reserved.