N-(9-fluorenylmethoxycarbonyl)-cis-3-(aminomethyl)cyclobutane carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(9-fluorenylmethoxycarbonyl)-cis-3-(aminomethyl)cyclobutane carboxylic acid
• 英文别名: cis-3-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]cyclobutanecarboxylic acid；3-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]cyclobutane-1-carboxylic acid
• 化学式: C₂₁H₂₁NO₄
• 分子量: 351.402
• InChiKey: BJFFZAFKQSTORF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(羟基甲基)-1-(苯基甲基)-2-哌啶酮 在 盐酸 、 氨 、 lithium 、 sodium carbonate 、 甲基磺酰氯 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 42.58h， 生成 N-(9-fluorenylmethoxycarbonyl)-cis-3-(aminomethyl)cyclobutane carboxylic acid
  参考文献：
  名称：

  [EN] ANGIOTENSIN-(1-7) ANALOGS AND METHODS RELATING THERETO
  [FR] ANALOGUES DE L'ANGIOTENSINE (1-7) ET PROCÉDÉS ASSOCIÉS

  摘要：

  提供了血管紧张素（1-7）类似物。这些类似物包含一种或多种非天然氨基酸顺式-3-(氨甲基)环丁烷羧酸（ACCA）的取代物。还提供了制备这种类似物的方法以及利用这种类似物作为治疗组合物治疗或预防各种疾病或病症的方法。

  公开号：

  WO2017100776A1

文献信息

• Stabilization of Angiotensin-(1–7) by key substitution with a cyclic non-natural amino acid
  作者：Anita Wester、Marc Devocelle、E. Ann Tallant、Mark C. Chappell、Patricia E. Gallagher、Francesca Paradisi

  DOI：10.1007/s00726-017-2471-9

  日期：2017.10

  Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide's therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural delta-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP 3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer.
• ANGIOTENSIN-(1-7) ANALOGS AND METHODS RELATING THERETO
  申请人：WAKE FOREST UNIVERSITY HEALTH SCIENCES

  公开号：US20200216499A1

  公开（公告）日：2020-07-09

  Angiotensin (1-7) analogs are provided. The analogs contain one or more substitutions with non-natural amino acid cis-3-(aminomethyl)cyclobutanecarboxylic acid (ACCA). Also provided are methods of making such analogs and methods for using such analogs as therapeutic compositions to treat or prevent various diseases or conditions.