(3-N-boc-氨基-2-氧代-2,3,4,5-四氢-苯并[b]氮杂革-1-基)-乙酸 | 103105-97-1

• 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: (3-N-boc-氨基-2-氧代-2,3,4,5-四氢-苯并[b]氮杂革-1-基)-乙酸
• 中文别名: [3-({[(2-甲基-2-丙基)氧基]羰基}氨基)-2-氧代-2,3,4,5-四氢-1H-1-苯并氮杂卓-1-基]乙酸
• 英文名称: 2-(3-(tert-butoxycarbonylamino)-2-oxo-2,3,4,5-tetrahydrobenzo[b]azepin-1-yl)acetic acid
• 英文别名: 2-(3-((tert-Butoxycarbonyl)amino)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-1-yl)acetic acid；2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-oxo-4,5-dihydro-3H-1-benzazepin-1-yl]acetic acid
• CAS: 103105-97-1
• 化学式: C₁₇H₂₂N₂O₅
• 分子量: 334.372
• InChiKey: OENYEYMNWZNKEX-UHFFFAOYSA-N

物化性质

• 沸点：
  603.6±55.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

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
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (R)-3-amino-4-(3,4-dichlorophenyl)-N-methylbutanamide 、 (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 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 以72%的产率得到tert-butyl [1-(2-{[(2R)-1-(3,4-dichlorophenyl)-4-(methylamino)-4-oxobutan-2-yl]amino}-2-oxoethyl)-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]carbamate
  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

• Non-peptidyl Ras farnesyl transferase inhibitors
  申请人：GENENTECH, INC.

  公开号：EP0763537A2

  公开（公告）日：1997-03-19

  Benzodiazepine derivatives are disclosed that act as potent inhibitors of ras farnesyl:protein transferase. Pharmaceutical compositions containing these benzodiazepines are provided for treatment of diseases for which inhibition of the ras farnesyl:protein transferase is indicated.

  本研究公开了苯并二氮杂卓衍生物，它们是ras法尼酰：蛋白转移酶的强效抑制剂。含有这些苯并二氮杂卓的药物组合物可用于治疗需要抑制ras法尼基转移酶的疾病。
• PREPARATION OF N-CYANODITHIOIMINO-CARBONATES AND 3-MERCAPTO-5-AMINO-1H-1,2,4-TRIAZOLE
  申请人：GENENTECH, INC.

  公开号：EP0698015A1

  公开（公告）日：1996-02-28
• US4473575A
  申请人：——

  公开号：US4473575A

  公开（公告）日：1984-09-25
• US5532359A
  申请人：——

  公开号：US5532359A

  公开（公告）日：1996-07-02
• US5843941A
  申请人：——

  公开号：US5843941A

  公开（公告）日：1998-12-01