3-[4-(3-Amino-2-hydroxy-propoxy)-3-ethyl-5-methyl-phenyl]-1-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-propan-1-one | 910637-76-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-[4-(3-Amino-2-hydroxy-propoxy)-3-ethyl-5-methyl-phenyl]-1-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-propan-1-one
• 英文别名: 3-[4-(3-amino-2-hydroxypropoxy)-3-ethyl-5-methylphenyl]-1-(3-ethyl-5,5-dimethyl-6,7-dihydro-4H-2-benzothiophen-1-yl)propan-1-one
• CAS: 910637-76-2
• 化学式: C₂₇H₃₉NO₃S
• 分子量: 457.678
• InChiKey: MFIBOJLZQZZFDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  羟基乙酸 、 3-[4-(3-Amino-2-hydroxy-propoxy)-3-ethyl-5-methyl-phenyl]-1-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-propan-1-one 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.17h， 生成 rac-N-(3-{2-ethyl-4-[3-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydrobenzo[c]thiophen-1-yl)-3-oxopropyl]-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
• 作为产物：
  描述：

  4,4-二甲基环己酮 在 盐酸 、 草酰氯 、 乙醇 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氨 、 水 、 氢气 、 叔丁基锂 、 sodium 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 氯仿 、 水 、 异丙醇 、 叔丁醇 、 正戊烷 为溶剂， -78.0~75.0 ℃ 、150.0 kPa 条件下， 反应 51.67h， 生成 3-[4-(3-Amino-2-hydroxy-propoxy)-3-ethyl-5-methyl-phenyl]-1-(3-ethyl-5,5-dimethyl-4,5,6,7-tetrahydro-benzo[c]thiophen-1-yl)-propan-1-one
  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

• Hydrogenated Benzo (C) Thiophene Derivatives as Immunomodulators
  申请人：Bolli Martin

  公开号：US20080176926A1

  公开（公告）日：2008-07-24

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

  该发明涉及新型噻吩衍生物，其制备以及其作为药用活性化合物的用途。这些化合物特别作为免疫抑制剂。
• HYDROGENATED BENZO (C) THIOPHENE DERIVATIVES AS IMMUNOMODULATORS
  申请人：Bolli Martin

  公开号：US20100204198A1

  公开（公告）日：2010-08-12

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

  该发明涉及新型噻吩衍生物，其制备及其作为药物活性化合物的用途。所述化合物特别作为免疫抑制剂。
• HYDOGRENATED BENZO[C]THIOPHENE DERIVATIVES AS IMMUNOMODULATORS
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1863787B1

  公开（公告）日：2011-05-25
• US7723378B2
  申请人：——

  公开号：US7723378B2

  公开（公告）日：2010-05-25
• US8039644B2
  申请人：——

  公开号：US8039644B2

  公开（公告）日：2011-10-18