EtO-Thiazole-Phe-NH2 | 218288-94-9

• 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: EtO-Thiazole-Phe-NH2
• CAS: 218288-94-9
• 化学式: C₁₄H₁₆N₂O₂S
• 分子量: 276.359
• InChiKey: JSBJFACMXQMTMG-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  65.21
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  EtO-Thiazole-Phe-NH2 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 lithium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 HO-Thiazole-Phe-Val-Pro-Oxazole-Thiazole-Pro-Leu-NH2
  参考文献：
  名称：

  Synthesis, Structure–Activity Analysis, and Biological Evaluation of Sanguinamide B Analogues

  摘要：

  We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only L- and D-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation. Testing of all conformer analogues showed that inclusion of an L- or D-Phe was a superior design element than incorporating the N-Me moiety that is often utilized to control macrocyclic conformation. Finally, we show that there is an ideal Phe residue (in this case L-Phe) for generating compounds that have the greatest inhibitory effect on bacterial motility. Our data support the hypothesis that the macrocyclic conformation is dictated by the benzyl moiety requiring a "pseudoequatorial" position, and all other energy considerations are secondary.

  DOI：

  10.1021/jo3017499
• 作为产物：
  描述：

  (S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionamide 在 劳森试剂 、 吡啶 、 potassium hydrogencarbonate 、 苯甲醚 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 EtO-Thiazole-Phe-NH2
  参考文献：
  名称：

  Synthesis, Structure–Activity Analysis, and Biological Evaluation of Sanguinamide B Analogues

  摘要：

  We report the first synthesis of sanguinamide B analogues. Substituting N-methylated (N-Me) amino acids, glycine (Gly), and L- or D-phenylalanine (Phe) into the backbone of sanguinamide B showed that only L- and D-Phe residues controlled the macrocycle conformation. The N-methylated and glycine analogues all had multiple conformations, whereas the L- and D-Phe derivatives only had a single conformation. Testing of all conformer analogues showed that inclusion of an L- or D-Phe was a superior design element than incorporating the N-Me moiety that is often utilized to control macrocyclic conformation. Finally, we show that there is an ideal Phe residue (in this case L-Phe) for generating compounds that have the greatest inhibitory effect on bacterial motility. Our data support the hypothesis that the macrocyclic conformation is dictated by the benzyl moiety requiring a "pseudoequatorial" position, and all other energy considerations are secondary.

  DOI：

  10.1021/jo3017499

文献信息

• Synthesis and evaluation of novel dolastatin 10 derivatives for versatile conjugations
  作者：Shinya Yokosaka、Akiko Izawa、Chizuka Sakai、Eri Sakurada、Yasuhiro Morita、Yukihiro Nishio

  DOI：10.1016/j.bmc.2018.02.011

  日期：2018.5

  several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative

  Dolastatin 10（1）是一种高效的细胞毒性微管抑制剂（细胞毒性IC 50  <5.0 nM），其几种类似物最近已被用作抗体药物偶联物中的有效载荷。在本文中，我们描述了一系列新颖的dolastatin 10类似物的设计和合成，这些类似物可用作结合药物的有效载荷。我们探索了在C的噻唑部分含有官能团的类似物-dolastatin 10的末端。官能团包括胺，醇和硫醇，它们是已知结合药物中使用的代表性结构。这些新颖的类似物在肿瘤细胞增殖试验中显示出出色的功效，因此，该系列的dolastatin 10类似物适合用作缀合药物中的通用有效负载。还讨论了对类似物的结构-活性关系的见解。
• Synthesis and antiproliferative activity of a cyclic analog of dolastatin 10
  作者：Joël Poncet、Laurent Hortala、Magali Busquet、Françoise Guéritte-Voegelein、Sylvie Thoret、Alain Pierré、Ghanem Atassi、Patrick Jouin

  DOI：10.1016/s0960-894x(98)00511-3

  日期：1998.10

  A cyclic analog of the natural antiproliferative compound dolastatin 10 was synthesized by introducing an ester link between the N- and C-terminal residues which were modified accordingly. The final macrolactonization was performed by using isopropenyl chloroformate and DMAP as reagents. This analog exhibits submicromolar antiproliferative activity against the L1210 and HT29 cell lines and inhibits in vitro tubulin polymerization (IC50, 39 mu M). (C) 1998 Elsevier Science Ltd. All lights reserved.