Fmoc-melphalan

• 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: Fmoc-melphalan
• 英文别名: Fmoc-4-bis(2-chloroethyl)amino-L-phenylalanine；(2S)-3-[4-[bis(2-chloroethyl)amino]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• 化学式: C₂₈H₂₈Cl₂N₂O₄
• 分子量: 527.447
• InChiKey: AVJVPROWJLZHME-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.51
• 重原子数：
  36.0
• 可旋转键数：
  11.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.87
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  Fmoc-melphalan 、 聚甘氨酸 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 46.0h， 生成
  参考文献：
  名称：

  Preparation, characterization, and in vitro efficacy of O-carboxymethyl chitosan conjugate of melphalan

  摘要：

  A series of melphalan-O-carboxymethyl chitosan (Mel-OCM-chitosan) conjugates with different spacers were prepared and structurally characterized. All conjugates showed satisfactory water-solubility (160-217 times of Mel solubility). In vitro drug release behaviors by both chemical and enzymatic hydrolysis were investigated. The prodrugs released Mel rapidly within papain and lysosomal enzymes of about 40-75%, while released only about 4-5% in buffer and plasma, which suggested that the conjugates have good plasma stability and the hydrolysis in both papain and lysosomes occurs mostly via enzymolysis. It was found that the spacers have important effect on the drug content, water solubility, drug release properties and cytotoxicity of Mel-OCM-chitosan conjugates. Cytotoxicity studies by MTT assay demonstrated that these conjugates had 52-70% of cytotoxicity against RPMI8226 cells in vitro as compared with free Mel, indicating the conjugates did not lose anti-cancer activity of Mel. Overall these studies indicated Mel-OCM-chitosan conjugates as potential prodrugs for cancer treatment. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carbpol.2013.04.071
• 作为产物：
  描述：

  美法仑 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 以 1,4-二氧六环 为溶剂， 生成 Fmoc-melphalan
  参考文献：
  名称：

  [EN] CONJUGATE OF CELL-PENETRATING PEPTIDE AND MELPHALAN, AND PREPARATION CONTAINING CONJUGATE
  [FR] CONJUGUÉ DE PEPTIDE DE PÉNÉTRATION CELLULAIRE ET DE MELPHALAN ET PRÉPARATION CONTENANT LE CONJUGUÉ
  [ZH] 穿膜肽与美法仑的偶联物以及包含该偶联物的制剂

  摘要：

  本发明涉及穿膜肽与美法仑的偶联物以及包含该偶联物的制剂。具体而言，本发明涉及穿膜肽衍生物与美法仑通过共价连接形成的偶联物、包含该偶联物的制剂、使用该偶联物治疗疾病的方法以及所述制剂在治疗疾病中的应用。

  公开号：

  WO2023001245A1

文献信息

• Substituted indoles and methods of their use
  申请人：Hu Baihua

  公开号：US20070043101A1

  公开（公告）日：2007-02-22

  The present invention relates generally to substituted indoles and methods of using them.

  本发明一般涉及替代吲哚化合物及其使用方法。
• Substituted Indoles And Methods Of Their Use
  申请人：HU Baihua

  公开号：US20100137363A1

  公开（公告）日：2010-06-03

  The present invention relates generally to substituted indoles and methods of using them.

  本发明涉及替代吲哚及其使用方法。
• Novel materials and methods for the treatment of Alzheimer's disease patients
  申请人：Smith O. Steven

  公开号：US20060062797A1

  公开（公告）日：2006-03-23

  The invention generally relates to the treatment of patients with Alzheimer's disease, at risk for Alzheimer's disease, and other neurodegenerative diseases. More specifically, embodiments of the present invention contemplate novel compositions and methods for the treatment of such patients. In one embodiment, the present invention contemplates proteins and protein variants that function by depolymerizing or preventing the polymerization of amyloid plaques believed to play a role in the etiology of Alzheimer's disease.

  本发明一般涉及阿尔茨海默病患者、有阿尔茨海默病风险的患者以及其他神经退行性疾病患者的治疗。更具体地说，本发明的实施方案考虑了治疗此类患者的新型组合物和方法。在一个实施方案中，本发明考虑了通过解聚或阻止淀粉样蛋白斑块的聚合来发挥作用的蛋白质和蛋白质变体，据信淀粉样蛋白斑块在阿尔茨海默病的病因学中起作用。
• Peptide inhibitors against seprase
  申请人：Chen Wen-Tien

  公开号：US20060172938A1

  公开（公告）日：2006-08-03

  The invention generally relates compositions and methods for the treatment of patients with melanoma and other malignant cancers. The compositions of the present invention are novel peptide sequences that inhibit seprase-mediated cell migration. Said sequences may also be used for diagnostics and library screening protocols.

  本发明一般涉及用于治疗黑色素瘤和其他恶性癌症患者的组合物和方法。本发明的组合物是抑制肽酶介导的细胞迁移的新型肽序列。所述序列还可用于诊断和文库筛选方案。
• A novel melphalan polymeric prodrug: Preparation and property study
  作者：Dan Li、Bo Lu、Zhijun Huang、Peihu Xu、Hua Zheng、Yihua Yin、Haixing Xu、Xia Liu、Lingyun Chen、Yiceng Lou、Xueqiong Zhang、Fuliang Xiong

  DOI：10.1016/j.carbpol.2014.04.062

  日期：2014.10

  The clinical application of melphalan (Me), an anticancer drug for the treatment of hematologic malignancies, has been limited due to its poor water solubility, rapid elimination and lack of target specificity. To solve these problems, O,N-carboxymethyl chitosan-peptide-melphalan conjugates were synthesized and characterized. All polymeric prodrugs showed satisfactory water solubility. It was found that the molecular weight of O,N-carboxymethyl chitosan (O,N-CMCS) and the peptide spacer played a crucial role in controlling the drug content, diameter and drug release properties of O,N-carboxymethyl chitosan-peptide-melphalan conjugates. The studies of in vitro drug release and cell cytotoxicity by MTT assay revealed that, employing the polymeric conjugation strategy and using the peptides glycylglycine (Gly-Gly) as a spacer, the conjugates have good cathepsin X-sensitivity and lower toxicity and the drug release behavior improved remarkably. In conclusion, O,N-carboxymethyl chitosan-peptide-melphalan conjugates could be promising prodrugs for anticancer application. (C) 2014 Elsevier Ltd. All rights reserved.