(R)-2-allyl-N4-(4-chlorobenzyl)-N1-((R)-2-hydroxy-2-phenylethyl)succinamide | 1201482-32-7

• 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: (R)-2-allyl-N4-(4-chlorobenzyl)-N1-((R)-2-hydroxy-2-phenylethyl)succinamide
• CAS: 1201482-32-7
• 化学式: C₂₂H₂₅ClN₂O₃
• 分子量: 400.905
• InChiKey: UDQMKULIZZWQCG-QUCCMNQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  78.43
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5-己烯酸 、 (R)-2-allyl-N4-(4-chlorobenzyl)-N1-((R)-2-hydroxy-2-phenylethyl)succinamide 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以67%的产率得到(R)-2-((R)-2-(2-((4-chlorobenzyl)amino)-2-oxoethyl)pent-4-enamido)-1-phenylethyl hex-5-enoate
  参考文献：
  名称：

  Syntheses of aminoalcohol-derived macrocycles leading to a small-molecule binder to and inhibitor of Sonic Hedgehog

  摘要：

  We report the synthesis and biological activity of a library of aminoalcohol-derived macrocycles from which robotnikinin (17), a binder to and inhibitor of Sonic Hedgehog, was derived. Using an asymmetric alkylation to set a key stereocenter and an RCM reaction to close the macrocycle, we were able to synthesize compounds for testing. High-throughput screening via small-molecule microarray (SMM) technology led to the discovery of a compound capable of binding ShhN. Follow-up chemistry led to a library of macrocycles with enhanced biological activity relative to the original hit compounds. Differences in ring size and stereochemistry, leading to alterations in the mode of binding, may account for differences in the degree of biological activity. These compounds are the first ones reported that inhibit Shh signaling at the ShhN level. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.089
• 作为产物：
  描述：

  (R)-2-(2-(4-chlorobenzylamino)-2-oxoethyl)pent-4-enoic acid 、 (R)-α-(氨基甲基)苄醇 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以91%的产率得到(R)-2-allyl-N4-(4-chlorobenzyl)-N1-((R)-2-hydroxy-2-phenylethyl)succinamide
  参考文献：
  名称：

  Syntheses of aminoalcohol-derived macrocycles leading to a small-molecule binder to and inhibitor of Sonic Hedgehog

  摘要：

  We report the synthesis and biological activity of a library of aminoalcohol-derived macrocycles from which robotnikinin (17), a binder to and inhibitor of Sonic Hedgehog, was derived. Using an asymmetric alkylation to set a key stereocenter and an RCM reaction to close the macrocycle, we were able to synthesize compounds for testing. High-throughput screening via small-molecule microarray (SMM) technology led to the discovery of a compound capable of binding ShhN. Follow-up chemistry led to a library of macrocycles with enhanced biological activity relative to the original hit compounds. Differences in ring size and stereochemistry, leading to alterations in the mode of binding, may account for differences in the degree of biological activity. These compounds are the first ones reported that inhibit Shh signaling at the ShhN level. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.089