Fmoc-Cys(CH2CH2CH2COOtBu)-O-All | 276869-37-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: Fmoc-Cys(CH2CH2CH2COOtBu)-O-All
• 英文别名: 4-[(2R)-allyloxycarbonyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethylsulfanyl]butyric acid tert butyl ester；tert-butyl 4-[(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-oxo-3-prop-2-enoxypropyl]sulfanylbutanoate
• CAS: 276869-37-5
• 化学式: C₂₉H₃₅NO₆S
• 分子量: 525.666
• InChiKey: GPNYNAIUJSYUBJ-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  37
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Fmoc-Cys(CH2CH2CH2COOtBu)-O-All 在 三氟乙酸 作用下， 反应 2.0h， 生成 Thiophene-2-carboxylic acid [(R)-1-benzylcarbamoyl-2-(3-hydroxycarbamoyl-propylsulfanyl)-ethyl]-amide
  参考文献：
  名称：

  Antiproliferative and Phenotype-Transforming Antitumor Agents Derived from Cysteine

  摘要：

  Selective destruction of malignant tumor cells without damaging normal cells is an important goal for cancer chemotherapy in the 21st century. Differentiating agents that transform cancer cells to either a nonproliferating or normal phenotype could potentially be tissue-specific and avoid side effects of current drugs. However, most compounds that are presently known to differentiate cancer cells are histone deacetylase inhibitors that are of low potency or suffer from low bioavailability, rapid metabolism, reversible differentiation, and nonselectivity for cancer cells over normal cells. Here we describe 36 nonpeptidic compounds derived from a simple cysteine scaffold, fused at the C-terminus to benzylamine, at the N-terminus to a small library of carboxylic acids, and at the S-terminus to 4-butanoyl hydroxamate. Six compounds were cytotoxic at nanomolar concentrations against a particularly aggressive human melanoma cell line (MM96L), four compounds showed selectivities of greater than or equal to5:1 for human melanoma over normal human cells (NFF), and four of the most potent compounds were further tested and found to be cytotoxic for six other human cancer cell lines (melanomas SK-MEL-28, DO4; prostate DU145; breast MCF-7; ovarian JAM, CI80-13S). The most active compounds typically caused hyperacetylation of histones, induced p21 expression, and reverted phenotype of surviving tumor cells to a normal morphology. Only one compound was given orally at 5 mg/kg to healthy rats to look for bioavailaiblity, and it showed reasonably high levels in plasma (C-max 6 mug/mL, T-max 15 min) for at least 4 h. Results are sufficiently promising to support further work on refining this and related classes of compounds to an orally active, more tumor-selective, antitumor drug.

  DOI：

  10.1021/jm030222i
• 作为产物：
  描述：

  4-碘丁酸叔丁酯 在 sodium hydroxide 、 碳酸氢钠 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 Fmoc-Cys(CH2CH2CH2COOtBu)-O-All
  参考文献：
  名称：

  Antiproliferative and Phenotype-Transforming Antitumor Agents Derived from Cysteine

  摘要：

  Selective destruction of malignant tumor cells without damaging normal cells is an important goal for cancer chemotherapy in the 21st century. Differentiating agents that transform cancer cells to either a nonproliferating or normal phenotype could potentially be tissue-specific and avoid side effects of current drugs. However, most compounds that are presently known to differentiate cancer cells are histone deacetylase inhibitors that are of low potency or suffer from low bioavailability, rapid metabolism, reversible differentiation, and nonselectivity for cancer cells over normal cells. Here we describe 36 nonpeptidic compounds derived from a simple cysteine scaffold, fused at the C-terminus to benzylamine, at the N-terminus to a small library of carboxylic acids, and at the S-terminus to 4-butanoyl hydroxamate. Six compounds were cytotoxic at nanomolar concentrations against a particularly aggressive human melanoma cell line (MM96L), four compounds showed selectivities of greater than or equal to5:1 for human melanoma over normal human cells (NFF), and four of the most potent compounds were further tested and found to be cytotoxic for six other human cancer cell lines (melanomas SK-MEL-28, DO4; prostate DU145; breast MCF-7; ovarian JAM, CI80-13S). The most active compounds typically caused hyperacetylation of histones, induced p21 expression, and reverted phenotype of surviving tumor cells to a normal morphology. Only one compound was given orally at 5 mg/kg to healthy rats to look for bioavailaiblity, and it showed reasonably high levels in plasma (C-max 6 mug/mL, T-max 15 min) for at least 4 h. Results are sufficiently promising to support further work on refining this and related classes of compounds to an orally active, more tumor-selective, antitumor drug.

  DOI：

  10.1021/jm030222i

文献信息

• 1-Deamino-1(15)-carba and -Dicarba Analogues of Endothelin-1
  作者：Jan Hlaváček、Renáta Marcová、Miloš Buděšínský、Jiřina Slaninová

  DOI：10.1135/cccc20000407

  日期：——

  Sulfanyl-methylene and ethylene bridges were inserted into the molecule of endothelin-1 (ET-1) as other possible isosteric replacements of its outer disulfide linkage. The [1-deamino-1-carba]ET-1, [1-deamino-15-carba]ET-1 and [1-deamino-1,15-dicarba]ET-1 were synthesized either by a fragment condensation of protected cyclic pentadecapeptides with carboxy-terminal hexapeptides of the endothelin-1 sequence or by step-wise coupling on polymer support of the entire henicosapeptide sequences from carboxy-terminus. The analogues were devoid of uterotonic activity in comparison with the parent ET-1.

  硫醇亚甲基和乙烯桥被插入内皮素-1（ET-1）分子中，作为其外部二硫键的其他可能的同位素替代物。通过保护的环状十五肽片段与内皮素-1序列的羧基末端六肽片段的片段缩合或通过聚合物支持的整个二十一肽序列的逐步耦合，合成了[1-去氨基-1-卡巴]ET-1，[1-去氨基-15-卡巴]ET-1和[1-去氨基-1,15-双卡巴]ET-1。与母体ET-1相比，这些类似物缺乏子宫收缩活性。
• Anti-Cancer Agents
  申请人：Fairlie David

  公开号：US20080004290A1

  公开（公告）日：2008-01-03

  The present invention provides compounds having the structural formula (I): and methods for the treatment of cancer using compounds of formula (I).

  本发明提供了具有结构式(I)的化合物，并使用结构式(I)化合物的方法来治疗癌症。