(S)-(3-N-Boc-氨基-2-氧代-2,3,4,5-四氢-苯并[b]氮杂革-1-基)-乙酸 | 94793-95-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: (S)-(3-N-Boc-氨基-2-氧代-2,3,4,5-四氢-苯并[b]氮杂革-1-基)-乙酸
• 英文名称: (S)-2-(3-((tert-butoxycarbonyl)amino)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)acetic acid
• 英文别名: {(3S)-3-[(tert-Butoxycarbonyl)amino]-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl}acetic acid；2-[(3S)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid
• CAS: 94793-95-0
• 化学式: C₁₇H₂₂N₂O₅
• 分子量: 334.372
• InChiKey: OENYEYMNWZNKEX-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (S)-(3-N-Boc-氨基-2-氧代-2,3,4,5-四氢-苯并[b]氮杂革-1-基)-乙酸 在 铑 作用下， 以 乙醇 为溶剂， 以to give 3-(S)-t-butyloxycarbonylamino-1-carboxymethyl-2,3,4,5,5a,6,7,8,9,9a-decahydro-1H-[1]benzazepin-2-one which的产率得到3-(S)-t-butyloxycarbonylamino-1-carboxymethyl-2,3,4,5,5a,6,7,8,9,9a-decahydro-1H-[1]benzazepin-2-one
  参考文献：
  名称：

  3-Amino-(1)-benzazepin-2-one-1-alkanoic acids

  摘要：

  不同取代的1-羧甲基-3-(羧甲基氨基)-2,3,4,5-四氢-1H-[1]苯并嗪-2-酮及其官能衍生物是肾素-血管紧张素转换酶抑制剂，可用作降压剂。本发明涉及该类化合物的合成、组合物和治疗方法。

  公开号：

  US04473575A1
• 作为产物：
  描述：

  (S)-3-氨基-2,3,4,5-四氢-2-氧-1H-1-苯并氮杂卓-1-乙酸叔丁酯 在 氯化亚砜 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 66.0h， 生成 (S)-(3-N-Boc-氨基-2-氧代-2,3,4,5-四氢-苯并[b]氮杂革-1-基)-乙酸
  参考文献：
  名称：

  Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors

  摘要：

  Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound 1, a 1.5 mu M Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound 1 bound to Mcl-1 in a beta-turn conformation, such that the two ends of the peptide were close together. This proximity allowed for the linking of the two ends of the peptide to form a macrocycle. Macrocyclization resulted in an approximately 10-fold improvement in binding potency. Further exploration of a key hydrophobic interaction with Mcl-1 protein and also with the moiety that engages Arg256 led to additional potency improvements. The use of protein-ligand crystal structures and binding kinetics contributed to the design and understanding of the potency gains. Optimized compound 26 is a <3 nM Mcl-1 inhibitor, while inhibiting Bcl-2;at only 5 mu M and Bcl-xL at >99 mu M, and induces cleaved caspase-3 in MV4-11 cells with an IC50 of 3 mu M after 6 h.

  DOI：

  10.1021/acsmedchemlett.6b00464

文献信息

• US4473575A
  申请人：——

  公开号：US4473575A

  公开（公告）日：1984-09-25