(S)-2-((1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-3-phenyl propanoic acid | 1260227-23-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-2-((1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-3-phenyl propanoic acid
• 英文别名: (2S)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-3-phenylpropanoic acid
• CAS: 1260227-23-3
• 化学式: C₁₇H₁₅BrF₃NO₂
• 分子量: 402.211
• InChiKey: UQRLTAYWIXGQPF-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-((1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-3-phenyl propanoic acid 、 (S)-2-氨基-3-苯基丙腈 在 2,6-二甲基吡啶 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-N-[(1S)-1-cyano-2-phenylethyl]-3-phenylpropanamide
  参考文献：
  名称：

  Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease

  摘要：

  Identification of potent and reversible cruzipain inhibitors for the treatment of Chagas disease is described. The identified inhibitors bearing an amino nitrile warhead in P1 exhibit low nanomolar in vitro potency against cruzipain. Further SAR in P2 portion led to the identification of compounds, such as 26, that have a unique selectivity profile against other cysteine proteases and offering new opportunities for safer treatment of Chagas disease. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.015
• 作为产物：
  描述：

  L-苯丙氨酸甲酯盐酸盐 在 zinc(II) tetrahydroborate 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 22.0h， 生成 (S)-2-((1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-3-phenyl propanoic acid
  参考文献：
  名称：

  半胱氨酸蛋白酶CPB的共价可逆抑制剂的合成和匹配的分子对分析。

  摘要：

  半胱氨酸蛋白酶B（CPB）可以被可逆的共价抑制剂作为目标，该抑制剂可以用作抗衰老化合物。此处，合成了十六种二肽基腈衍生物，针对CPB进行了测试，并使用匹配的分子对进行了分析，以确定立体化学和对苯基取代对酶抑制的影响。化合物（S）-2-（（（（S）-1-（4-溴苯基）-2,2,2-三氟乙基）氨基）-N-（1-氰基环丙基）-3-苯基丙酰胺（5）最多强大的CPB抑制剂（pKi = 6.82），对人组织蛋白酶B也具有选择性（pKi <5）。当置于P2位置而不是P3时，立体化学从S到R的转化对效能的损害更大。该p-Br衍生物比p -CH 3和p -OCH 3衍生物更有效，可能是由于与S3亚位点的分子间相互作用。

  DOI：

  10.1016/j.bmcl.2020.127439

文献信息

• Synthesis and structure-activity relationship of nitrile-based cruzain inhibitors incorporating a trifluoroethylamine-based P2 amide replacement
  作者：Juliana C. Gomes、Lorenzo Cianni、Jean Ribeiro、Fernanda dos Reis Rocho、Samelyn da Costa Martins Silva、Pedro Henrique Jatai Batista、Carolina Borsoi Moraes、Caio Haddad Franco、Lucio H.G. Freitas-Junior、Peter W. Kenny、Andrei Leitão、Antonio C.B. Burtoloso、Daniela de Vita、Carlos A. Montanari

  DOI：10.1016/j.bmc.2019.115083

  日期：2019.11

  The structure-activity relationship for nitrile-based cruzain inhibitors incorporating a P2 amide replacement based on trifluoroethylamine was explored by deconstruction of a published series of inhibitors. It was demonstrated that the P3 biphenyl substituent present in the published inhibitor structures could be truncated to phenyl with only a small loss of affinity. The effects of inverting the configuration of the P2 amide replacement and linking a benzyl substituent at P1 were observed to be strongly nonadditive. We show that plotting affinity against molecular size provides a means to visualize both the molecular size efficiency of structural transformations and the nonadditivity in the structure-activity relationship. We also show how the relationship between affinity and lipophilicity, measured by high-performance liquid chromatography with an immobilized artificial membrane stationary phase, may be used to normalize affinity with respect to lipophilicity.