(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
• Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors
  作者：Jeffrey W. Johannes、Stephanie Bates、Carl Beigie、Matthew A. Belmonte、John Breen、Shenggen Cao、Paolo A. Centrella、Matthew A. Clark、John W. Cuozzo、Christoph E. Dumelin、Andrew D. Ferguson、Sevan Habeshian、David Hargreaves、Camil Joubran、Steven Kazmirski、Anthony D. Keefe、Michelle L. Lamb、Haiye Lan、Yunxia Li、Hao Ma、Scott Mlynarski、Martin J. Packer、Philip B. Rawlins、Daniel W. Robbins、Haidong Shen、Eric A. Sigel、Holly H. Soutter、Nancy Su、Dawn M. Troast、Haiyun Wang、Kate F. Wickson、Chengyan Wu、Ying Zhang、Qiuying Zhao、Xiaolan Zheng、Alexander W. Hird

  DOI：10.1021/acsmedchemlett.6b00464

  日期：2017.2.9

  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.
• 3-Amino-(1)-benzazepin-2-one-1-alkanoic acids
  申请人：Ciba-Geigy Corporation

  公开号：US04473575A1

  公开（公告）日：1984-09-25

  Variously substituted 1-carboxymethyl-3-(carboxymethylamino)-2,3,4,5-tetrahydro-1H-[1]benzazepin -2-ones and functional derivatives are angiotensin converting enzyme inhibitors and are useful as antihypertensive agents. Synthesis of, compositions and methods of treatment utilizing such compounds are included.

  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。