N-Cbz-Phe-Lys(ε-Alloc)-4-aminobenzyl 4-nitrophenyl carbonate | 159857-90-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-Cbz-Phe-Lys(ε-Alloc)-4-aminobenzyl 4-nitrophenyl carbonate
• 英文别名: (4-Nitrophenyl) [4-[[(2S)-2-[[(2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]-6-(prop-2-enoxycarbonylamino)hexanoyl]amino]phenyl]methyl carbonate
• CAS: 159857-90-6
• 化学式: C₄₁H₄₃N₅O₁₁
• 分子量: 781.819
• InChiKey: WCMFRXGMKLCNDT-ZPGRZCPFSA-N

物化性质

• 沸点：
  1013.2±65.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  57
• 可旋转键数：
  23
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  216
• 氢给体数：
  4
• 氢受体数：
  11

制备方法与用途

生物活性

Cbz-Phe-(Alloc)Lys-PAB-PNP 是可用于抗体偶联药物 (ADC) 的可降解 linker。

靶点

Cleavable

反应信息

• 作为反应物：
  描述：

  N-Cbz-Phe-Lys(ε-Alloc)-4-aminobenzyl 4-nitrophenyl carbonate 在 吗啉 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 生成 Benzyloxycarbonyl-L-phenylalanyl-L-lysyl-PABC-4-fluorodeacetylcolchicine
  参考文献：
  名称：

  Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B

  摘要：

  Novel colchicine derivatives possessing various substituents at the C4 position were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher activity against cancer cell lines (A549, HT29, HCT116) as well as on mice transplanted with the HCT116 human colorectal carcinoma cell line than colchicine (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs having a dipeptide side chain and demonstrated that these pro-drugs were activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited selective toxicity to the tumor cells.

  DOI：

  10.1021/ml100287y
• 作为产物：
  描述：

  L-赖氨酸 在 N-甲基吗啉 、 吡啶 、 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 生成 N-Cbz-Phe-Lys(ε-Alloc)-4-aminobenzyl 4-nitrophenyl carbonate
  参考文献：
  名称：

  Design, Synthesis, and Antitumor Activity of 4-Halocolchicines and Their Pro-drugs Activated by Cathepsin B

  摘要：

  Novel colchicine derivatives possessing various substituents at the C4 position were prepared. Among them, 4-halo derivatives 3-6 were found to exhibit higher activity against cancer cell lines (A549, HT29, HCT116) as well as on mice transplanted with the HCT116 human colorectal carcinoma cell line than colchicine (1). Further, utilizing the 4-substituted colchicines, we prepared pro-drugs having a dipeptide side chain and demonstrated that these pro-drugs were activated by cathepsin B, an enzyme overexpressed in tumor cells, and exhibited selective toxicity to the tumor cells.

  DOI：

  10.1021/ml100287y

文献信息

• [EN] CONJUGATE COMPOUNDS<br/>[FR] COMPOSÉS CONJUGUÉS
  申请人：CALLAGHAN INNOVATION RES LTD

  公开号：WO2014088432A1

  公开（公告）日：2014-06-12

  The invention relates to sphingoglycolipid analogues and peptide derivatives thereof, which are useful in treating or preventing diseases or such as those relating to infection, atopic disorders, autoimmune diseases or cancer.

  这项发明涉及鞘氨醇糖脂类似物及其肽衍生物，可用于治疗或预防与感染、特应性疾病、自身免疫疾病或癌症相关的疾病。
• Cathepsin B-sensitive dipeptide prodrugs. 2. Models of anticancer drugs paclitaxel (Taxol®), mitomycin C and doxorubicin
  作者：Gene M. Dubowchik、Kathleen Mosure、Jay O. Knipe、Raymond A. Firestone

  DOI：10.1016/s0960-894x(98)00610-6

  日期：1998.12

  Substrates containing doxorubicin (DOX), paclitaxel (taxol), and mitomycin C (MMC) attached to the cathepsin B-sensitive dipeptide Phe-Lys via a self-immolative spacer were prepared as model compounds for internalizing anticancer immunoconjugates. Cathepsin B-mediated release rates of free drug, rat liver lysosomal susceptibility and human plasma stability were measured for each.

  制备了包含阿霉素（DOX），紫杉醇（紫杉醇）和丝裂霉素C（MMC）并通过自消灭性间隔子连接到组织蛋白酶B敏感二肽Phe-Lys的底物，作为用于内化抗癌免疫偶联物的模型化合物。分别测量组织蛋白酶B介导的游离药物释放速率，大鼠肝溶酶体敏感性和人血浆稳定性。
• Dubowchik, Gene M.; Firestone, Raymond A., Bioorganic and medicinal chemistry letters, 1998, vol. 8, # 23, p. 3343 - 3346
  作者：Dubowchik, Gene M.、Firestone, Raymond A.

  DOI：——

  日期：——