methyl N-(((S)-2-((S)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanamido)-3-cyclohexylpropanoyl)-L-valyl)-N-methyl-D-phenylalanyl-L-phenylalaninate | 1010106-79-2

• 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: methyl N-(((S)-2-((S)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanamido)-3-cyclohexylpropanoyl)-L-valyl)-N-methyl-D-phenylalanyl-L-phenylalaninate
• CAS: 1010106-79-2
• 化学式: C₄₉H₆₇N₅O₉
• 分子量: 870.099
• InChiKey: IFWAVKSSHOEILH-DNOUOQLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.66
• 重原子数：
  63.0
• 可旋转键数：
  21.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  181.47
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  methyl N-(((S)-2-((S)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanamido)-3-cyclohexylpropanoyl)-L-valyl)-N-methyl-D-phenylalanyl-L-phenylalaninate 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 盐酸 、 苯甲醚 、 N,N-二异丙基乙胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 生成 cyclo[Cha-Val-D-N(Me)Phe-Phe-Ser(Bn)]
  参考文献：
  名称：

  Comprehensive Study of Sansalvamide A Derivatives and their Structure–Activity Relationships against Drug-Resistant Colon Cancer Cell Lines

  摘要：

  We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating, multiple drug-resistant colon cancers.

  DOI：

  10.1021/jm070731a
• 作为产物：
  描述：

  H-Val-D-N(Me)Phe-Phe-OMe 、 (S)-2-((S)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanamido)-3-cyclohexylpropanoic acid 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 methyl N-(((S)-2-((S)-3-(benzyloxy)-2-((tert-butoxycarbonyl)amino)propanamido)-3-cyclohexylpropanoyl)-L-valyl)-N-methyl-D-phenylalanyl-L-phenylalaninate
  参考文献：
  名称：

  Comprehensive Study of Sansalvamide A Derivatives and their Structure–Activity Relationships against Drug-Resistant Colon Cancer Cell Lines

  摘要：

  We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the key 3D features of potent compounds. Of the seven most potent compounds reported here, five are second-generation, emphasizing our ability to incorporate potent features found in the first generation and utilize their structures to design potency into the second generation. These analogs share no structural homology to current colon cancer drugs, are cytotoxic at levels on par with existing drugs treating other cancers, and demonstrate selectivity for drug-resistant colon cancer cell lines over noncancerous cell lines. Thus, we have established sansalvamide A as an excellent lead for treating, multiple drug-resistant colon cancers.

  DOI：

  10.1021/jm070731a

文献信息

• A comprehensive study of Sansalvamide A derivatives: The structure–activity relationships of 78 derivatives in two pancreatic cancer cell lines
  作者：Po-Shen Pan、Robert C. Vasko、Stephanie A. Lapera、Victoria A. Johnson、Robert P. Sellers、Chun-Chieh Lin、Chung-Mao Pan、Melinda R. Davis、Veronica C. Ardi、Shelli R. McAlpine

  DOI：10.1016/j.bmc.2009.07.017

  日期：2009.8

  first report of their activity against two pancreatic cancer cell lines. Our results show that out of 78 compounds, three compounds are worth pursuing as leads, as they show potency of ⩾55% in both cancer cell lines. These three compounds all have a common structural motif, two consecutive d-amino acids and an N-methyl moiety. Further, of these three compounds, two are second-generation structures, indicating

  我们报告了对两种胰腺癌细胞系有活性的 78 种化合物的广泛构效关系 (SAR)。我们对这些化合物的综合评估利用 SAR，使我们能够评估有效化合物的哪些特征对其细胞毒性起关键作用。这是 19 种新的第二代结构的首次报告，其中这些新化合物是从第一代 59 种化合物中设计出来的。测试了这 78 个结构的细胞毒性，这是它们对两种胰腺癌细胞系的活性的首次报告。我们的结果表明，在 78 种化合物中，有 3 种化合物值得作为先导物进行研究，因为它们在两种癌细胞系中都显示出 55% 的效力。这三种化合物都有一个共同的结构基序，两个连续的d-氨基酸和一个N-甲基部分。此外，在这三种化合物中，有两种是第二代结构，这表明我们可以合并和利用第一代的数据来设计第二代的效力。最后，一种类似物在中等纳摩尔范围内，并且在所有报道的 SAn A 衍生物中具有最低的 IC 50。这些类似物与当前的胰腺癌药物没有结构同源性，并