(E)-3-(2,6-dimethyl-4-((E)-3-oxo-3-(3,5,5-trimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-1-yl)prop-1-en-1-yl)phenyl)acrylic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(2,6-dimethyl-4-((E)-3-oxo-3-(3,5,5-trimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-1-yl)prop-1-en-1-yl)phenyl)acrylic acid
• 英文别名: 3-{2,6-dimethyl-4-[3-oxo-3-(3,5,5-trimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-propenyl]-phenyl}-acrylic acid；(E)-3-[2,6-dimethyl-4-[(E)-3-oxo-3-(3,5,5-trimethyl-6,7-dihydro-4H-2-benzothiophen-1-yl)prop-1-enyl]phenyl]prop-2-enoic acid
• 化学式: C₂₅H₂₈O₃S
• 分子量: 408.562
• InChiKey: UIAHRDSGXSYOOE-CDJQDVQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(2,6-dimethyl-4-((E)-3-oxo-3-(3,5,5-trimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-1-yl)prop-1-en-1-yl)phenyl)acrylic acid 在 palladium 10% on activated carbon 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 水 为溶剂， 50.0~60.0 ℃ 、1.0 MPa 条件下， 反应 168.0h， 以78%的产率得到3-(2,6-dimethyl-4-(3-oxo-3-(3,5,5-trimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-1-yl)propyl)phenyl)propanoic acid
  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
• 作为产物：
  描述：

  4,4-二甲基环己酮 在 草酰氯 、 乙醇 、 potassium tert-butylate 、 水 、 叔丁基锂 、 sodium 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 氯仿 、 叔丁醇 、 正戊烷 为溶剂， 反应 22.58h， 生成 (E)-3-(2,6-dimethyl-4-((E)-3-oxo-3-(3,5,5-trimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-1-yl)prop-1-en-1-yl)phenyl)acrylic acid
  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 Thiophene Derivatives
  申请人：Bolli Martin

  公开号：US20080300294A1

  公开（公告）日：2008-12-04

  The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.

  本发明涉及新型噻吩衍生物，其制备和用作药物活性化合物。所述化合物特别作为免疫抑制剂。
• NOVEL THIOPHENE DERIVATIVES
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1954688A1

  公开（公告）日：2008-08-13
• US7981924B2
  申请人：——

  公开号：US7981924B2

  公开（公告）日：2011-07-19
• [EN] NOVEL THIOPHENE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE THIOPHÈNE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2007060626A1

  公开（公告）日：2007-05-31

  [EN] The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.
  [FR] L'invention concerne de nouveaux dérivés de thiophène, leur préparation et leur utilisation comme composés pharmaceutiquement actifs. Lesdits composés agissent en particulier comme des immunosuppresseurs.
• 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.