(2E,4R)-N-[(1S)-4-carbamimidamido-1-{[(1S)-1-carbamoyl-2-(1H-indol-3-yl)ethyl]carbamoyl}butyl]-5-[(2S)-2-[(4-fluorophenyl)formamido]-3-phenylpropanamido]-4-hydroxy-2-(2-methylpropyl)pent-2-enamide | 1085965-82-7

• 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: (2E,4R)-N-[(1S)-4-carbamimidamido-1-{[(1S)-1-carbamoyl-2-(1H-indol-3-yl)ethyl]carbamoyl}butyl]-5-[(2S)-2-[(4-fluorophenyl)formamido]-3-phenylpropanamido]-4-hydroxy-2-(2-methylpropyl)pent-2-enamide
• 英文别名: N-[(2S)-1-[[(E,2R)-4-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]carbamoyl]-2-hydroxy-6-methylhept-3-enyl]amino]-1-oxo-3-phenylpropan-2-yl]-4-fluorobenzamide
• CAS: 1085965-82-7
• 化学式: C₄₂H₅₂FN₉O₆
• 分子量: 797.93
• InChiKey: ZDPCJJXVDVOFRD-MZNXXXKPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  58
• 可旋转键数：
  21
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  260
• 氢给体数：
  9
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2E,4R)-N-[(1S)-4-carbamimidamido-1-{[(1S)-1-carbamoyl-2-(1H-indol-3-yl)ethyl]carbamoyl}butyl]-5-[(2S)-2-[(4-fluorophenyl)formamido]-3-phenylpropanamido]-4-hydroxy-2-(2-methylpropyl)pent-2-enamide 在 氢气 、 palladium diacetate 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以29%的产率得到(2S,4R)-N-[(1S)-4-carbamimidamido-1-{[(1S)-1-carbamoyl-2-(1H-indol-3-yl)ethyl]carbamoyl}butyl]-5-[(2S)-2-[(4-fluorophenyl)formamido]-3-phenylpropanamido]-4-hydroxy-2-(2-methylpropyl)pentanamide
  参考文献：
  名称：

  Development of Novel G-Protein-Coupled Receptor 54 Agonists with Resistance to Degradation by Matrix Metalloproteinase

  摘要：

  Kisspeptin-GPR54 signaling is involved in the suppression of cancer metastasis and regulation of hormonal secretion. Recently, matrix metalloproteinase mediated deactivation of kisspeptins through hydrolysis of the Gly-Leu peptide bond has been reported. In the present report, GPR54 agonistic peptides having several nonhydrolyzable Gly-Leu dipeptide isosteres were designed and synthesized. (E)-Alkene- and hydroxyethylene-type isostere-containing analogues maintained the original activity with higher stability in murine serum and resistance to MMP-9-mediated cleavage.

  DOI：

  10.1021/jm800930w

文献信息

• METASTIN DERIVATIVE AND USE THEREOF
  申请人：Fujii Nobutaka

  公开号：US20110039786A1

  公开（公告）日：2011-02-17

  The present invention provides a metastin derivative represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, or a pharmaceutical composition containing it. The metastin derivative or a salt thereof is superior in blood stability, and has a cancer metastasis suppressive action or cancer growth suppressive action.

  本发明提供了一种由式(I)表示的metastin衍生物，其中每个符号如规范中所定义，或其盐，或含有其的药物组合物。该metastin衍生物或其盐具有较好的血液稳定性，并具有抑制癌转移或抑制癌细胞生长的作用。
• Development of Novel G-Protein-Coupled Receptor 54 Agonists with Resistance to Degradation by Matrix Metalloproteinase
  作者：Kenji Tomita、Shinya Oishi、Hiroaki Ohno、Stephen C. Peiper、Nobutaka Fujii

  DOI：10.1021/jm800930w

  日期：2008.12.11

  Kisspeptin-GPR54 signaling is involved in the suppression of cancer metastasis and regulation of hormonal secretion. Recently, matrix metalloproteinase mediated deactivation of kisspeptins through hydrolysis of the Gly-Leu peptide bond has been reported. In the present report, GPR54 agonistic peptides having several nonhydrolyzable Gly-Leu dipeptide isosteres were designed and synthesized. (E)-Alkene- and hydroxyethylene-type isostere-containing analogues maintained the original activity with higher stability in murine serum and resistance to MMP-9-mediated cleavage.