(2S)-2-amino-3-(tritylamino)propanoic acid | 1357107-75-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2S)-2-amino-3-(tritylamino)propanoic acid
• CAS: 1357107-75-5
• 化学式: C₂₂H₂₂N₂O₂
• 分子量: 346.429
• InChiKey: HETXAESTAVRDLM-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  75.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-3-(tritylamino)propanoic acid 、 N-芴甲氧羰基-L-丙氨酸琥珀酰亚胺酯 在 碳酸氢钠 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 Fmoc-Ala-Asn(Trt)-OH
  参考文献：
  名称：

  肽硫酸的催化一步合成：通过反复的肽-片段偶联反应合成亮丙瑞林†

  摘要：

  开发了一种催化一步合成肽硫代酸的方法。氧-硫原子交换反应将肽C-末端的羧基转化为差向异构化的硫代羧基。该方法已通过迭代片段偶联方案成功应用于肽药物亮丙瑞林的合成。

  DOI：

  10.1039/c8cc07935h
• 作为产物：
  描述：

  (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(tritylamino)propanoic acid 在 哌啶 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以89%的产率得到(2S)-2-amino-3-(tritylamino)propanoic acid
  参考文献：
  名称：

  Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity

  摘要：

  The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-L-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit K-i(aPP) <= 10 nM and GI(50) approximate to 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.

  DOI：

  10.1021/jm201195m

文献信息

• Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity
  作者：Fang Wang、James A. D. Good、Oliver Rath、Hung Yi Kristal Kaan、Oliver B. Sutcliffe、Simon P. Mackay、Frank Kozielski

  DOI：10.1021/jm201195m

  日期：2012.2.23

  The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-L-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit K-i(aPP) <= 10 nM and GI(50) approximate to 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.
• A catalytic one-step synthesis of peptide thioacids: the synthesis of leuprorelin <i>via</i> iterative peptide–fragment coupling reactions
  作者：Takuya Matsumoto、Koki Sasamoto、Ryo Hirano、Kounosuke Oisaki、Motomu Kanai

  DOI：10.1039/c8cc07935h

  日期：——

  A catalytic one-step synthesis of peptide thioacids was developed. The oxygen–sulfur atom exchange reaction converted the carboxy group at the C-terminus of the peptides into a thiocarboxy group with suppressed epimerization. This method was successfully applied to the synthesis of the peptide drug leuprorelin via an iterative fragment-coupling protocol.

  开发了一种催化一步合成肽硫代酸的方法。氧-硫原子交换反应将肽C-末端的羧基转化为差向异构化的硫代羧基。该方法已通过迭代片段偶联方案成功应用于肽药物亮丙瑞林的合成。