{[3-HQA-D-Dap(Me1)-Gly-NMe-Cys(2)-NMe-Cys(Me)3][3-HQA-D-Dap(Me3)-Gly-NMe-Cys(2)-NMe-Cys(Me)1]} | 1114544-27-2

• 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: {[3-HQA-D-Dap(Me1)-Gly-NMe-Cys(2)-NMe-Cys(Me)3][3-HQA-D-Dap(Me3)-Gly-NMe-Cys(2)-NMe-Cys(Me)1]}
• 英文别名: NMe-azathiocoraline；3-hydroxy-N-[(1R,7R,11R,14R,20R,24R)-20-[(3-hydroxyquinoline-2-carbonyl)amino]-2,9,12,15,22,25-hexamethyl-11,24-bis(methylsulfanylmethyl)-3,6,10,13,16,19,23,26-octaoxo-28,29-dithia-2,5,9,12,15,18,22,25-octazabicyclo[12.12.4]triacontan-7-yl]quinoline-2-carboxamide
• CAS: 1114544-27-2
• 化学式: C₅₀H₆₂N₁₂O₁₂S₄
• 分子量: 1151.38
• InChiKey: YCQHTDAMXMBTPC-XYTQFZDWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  78
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  406
• 氢给体数：
  6
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  、 3-羟基喹啉-2-羧酸 在 N-羟基丁二酰亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 20.25h， 生成 {[3-HQA-D-Dap(Me1)-Gly-NMe-Cys(2)-NMe-Cys(Me)3][3-HQA-D-Dap(Me3)-Gly-NMe-Cys(2)-NMe-Cys(Me)1]}
  参考文献：
  名称：

  NMe Amide as a Synthetic Surrogate for the Thioester Moiety in Thiocoraline

  摘要：

  Bridged N-methyl amides are used as isosteres for depsi and thiodepsi bonds in thiocoraline. The introduction of NMe-amides in bridges mimics the thioester bonds without imposing steric hindrance and allows conservation of the hydrogen bonding map of the natural product. NMe-azathiocoraline was constructed by solid-phase N-methylation of the side chain of diaminopropionic acid (Dap). The three consecutive N-methyl amino acids could be coupled in good yields by using HATU/HOAt/DIEA in DMF, and the final octapeptide was also obtained on solid phase following a 4 + 4 fragment coupling approach. NMe-azathiocoraline (NMA) displayed nanomolar activity in the same order as the natural product and the same mode of action. In fact, modeling of NMe-azathiocoraline bonded to a TCGA sequence showed how the methyl groups remained further away from the DNA strand without changing the recognition pattern of thiocoraline. Moreover, NMe-azathiocoraline displayed an increased stability in human serum as compared to the parent natural product. This approach could be used in other depsipeptides and side chain to side chain cyclic peptides.

  DOI：

  10.1021/jm800784k

文献信息

• ANTITUMORAL COMPOUNDS
  申请人：PHARMA MAR, S.A.

  公开号：EP2231695B1

  公开（公告）日：2013-02-13
• Antitumoral Compounds
  申请人：Tulla-Puche Judit

  公开号：US20100292163A1

  公开（公告）日：2010-11-18

  Antitumoral compounds of Formula I, and pharmaceutically acceptable salts, derivatives, tautomers, prodrugs or stereoisomers thereof useful as antitumour agents.
• US8748388B2
  申请人：——

  公开号：US8748388B2

  公开（公告）日：2014-06-10
• [EN] ANTITUMORAL COMPOUNDS<br/>[FR] COMPOSÉS ANTITUMORAUX
  申请人：PHARMA MAR SA

  公开号：WO2009077401A1

  公开（公告）日：2009-06-25

  Antitumoral compounds of Formula (I), and pharmaceutically acceptable salts, derivatives, tautomers, prodrugs or stereoisomers thereof Formula (I) useful as antitumour agents.
• <i>N</i>Me Amide as a Synthetic Surrogate for the Thioester Moiety in Thiocoraline
  作者：Judit Tulla-Puche、Eleonora Marcucci、Elisabet Prats-Alfonso、Núria Bayó-Puxan、Fernando Albericio

  DOI：10.1021/jm800784k

  日期：2009.2.12

  Bridged N-methyl amides are used as isosteres for depsi and thiodepsi bonds in thiocoraline. The introduction of NMe-amides in bridges mimics the thioester bonds without imposing steric hindrance and allows conservation of the hydrogen bonding map of the natural product. NMe-azathiocoraline was constructed by solid-phase N-methylation of the side chain of diaminopropionic acid (Dap). The three consecutive N-methyl amino acids could be coupled in good yields by using HATU/HOAt/DIEA in DMF, and the final octapeptide was also obtained on solid phase following a 4 + 4 fragment coupling approach. NMe-azathiocoraline (NMA) displayed nanomolar activity in the same order as the natural product and the same mode of action. In fact, modeling of NMe-azathiocoraline bonded to a TCGA sequence showed how the methyl groups remained further away from the DNA strand without changing the recognition pattern of thiocoraline. Moreover, NMe-azathiocoraline displayed an increased stability in human serum as compared to the parent natural product. This approach could be used in other depsipeptides and side chain to side chain cyclic peptides.