N-((S)-3-{2-ethyl-4-[5-(3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-((S)-3-{2-ethyl-4-[5-(3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamide
• 英文别名: N-[(2S)-3-[2-ethyl-4-[5-(3-methoxy-5,5-dimethyl-6,7-dihydro-4H-2-benzothiophen-1-yl)-1,2,4-oxadiazol-3-yl]-6-methylphenoxy]-2-hydroxypropyl]-2-hydroxyacetamide
• 化学式: C₂₇H₃₅N₃O₆S
• 分子量: 529.657
• InChiKey: WOOOCCMCMKVQTL-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4,4-二甲基环己酮 在 N-碘代丁二酰亚胺 、 草酰氯 、 (CuOTf)*toluene 、 乙醇 、 potassium tert-butylate 、 水 、 sodium 、 1-羟基苯并三唑 、 caesium carbonate 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 75.58h， 生成 N-((S)-3-{2-ethyl-4-[5-(3-methoxy-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-[1,2,4]oxadiazol-3-yl]-6-methylphenoxy}-2-hydroxypropyl)-2-hydroxyacetamide
  参考文献：
  名称：

  Novel S1P₁ Receptor Agonists - Part 2: From Bicyclo[3.1.0]hexane-Fused Thiophenes to Isobutyl Substituted Thiophenes

  摘要：

  Previously, we reported on the discovery of a novel series of bicyclo[3.1.0]hexane fused thiophene derivatives that serve as potent and selective S1P(1), receptor agonists. Here, we discuss our efforts to simplify the bicyclohexane fused thiophene head. In a first step the bicyclohexane moiety could be replaced by a simpler, less rigid cyclohexane ring without compromising the SIP receptor affinity profile of these novel compounds. In a second step, the thiophene head was simplified even further by replacing the cyclohexane ring with an isobutyl group attached either to position 4 or position S of the thiophene. These structurally much simpler headgroups again furnished potent and selective S1P(1) agonists (e.g., 87), which efficiently and dose dependently reduced the number of circulating lymphocytes upon oral administration to male Wistar rats. For several compounds discussed in this report lymphatic transport is an important route of absorption that may offer opportunities for a tissue targeted approach with minimal plasma exposure.

  DOI：

  10.1021/jm401456d

文献信息

• Novel S1P₁ Receptor Agonists - Part 2: From Bicyclo[3.1.0]hexane-Fused Thiophenes to Isobutyl Substituted Thiophenes
  作者：Martin H. Bolli、Jörg Velker、Claus Müller、Boris Mathys、Magdalena Birker、Roberto Bravo、Daniel Bur、Ruben de Kanter、Patrick Hess、Christopher Kohl、David Lehmann、Solange Meyer、Oliver Nayler、Markus Rey、Michael Scherz、Beat Steiner

  DOI：10.1021/jm401456d

  日期：2014.1.9

  Previously, we reported on the discovery of a novel series of bicyclo[3.1.0]hexane fused thiophene derivatives that serve as potent and selective S1P(1), receptor agonists. Here, we discuss our efforts to simplify the bicyclohexane fused thiophene head. In a first step the bicyclohexane moiety could be replaced by a simpler, less rigid cyclohexane ring without compromising the SIP receptor affinity profile of these novel compounds. In a second step, the thiophene head was simplified even further by replacing the cyclohexane ring with an isobutyl group attached either to position 4 or position S of the thiophene. These structurally much simpler headgroups again furnished potent and selective S1P(1) agonists (e.g., 87), which efficiently and dose dependently reduced the number of circulating lymphocytes upon oral administration to male Wistar rats. For several compounds discussed in this report lymphatic transport is an important route of absorption that may offer opportunities for a tissue targeted approach with minimal plasma exposure.