(4R,5R)-N-[(4-methoxyphenyl)methyl]-4-[methyl-[(E,2R)-2-methyl-4-phenylbut-3-enyl]amino]-5-(2-methylpropoxy)azepane-1-carboxamide | 392724-84-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4R,5R)-N-[(4-methoxyphenyl)methyl]-4-[methyl-[(E,2R)-2-methyl-4-phenylbut-3-enyl]amino]-5-(2-methylpropoxy)azepane-1-carboxamide
• CAS: 392724-84-4
• 化学式: C₃₁H₄₅N₃O₃
• 分子量: 507.717
• InChiKey: LXTMLCXRXCIMAQ-GUOMTUETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  54
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4R,5R)-N-[(4-methoxyphenyl)methyl]-4-[methyl-[(E,2R)-2-methyl-4-phenylbut-3-enyl]amino]-5-(2-methylpropoxy)azepane-1-carboxamide 在 三氟化硼乙醚 、 二甲基二环氧乙烷 作用下， 以 乙醚 、 二氯甲烷 、 丙酮 为溶剂， 反应 1.5h， 以20%的产率得到(4R,5R)-N-[(4-methoxyphenyl)methyl]-4-[methyl-[(2S)-2-[(2S,3S)-3-phenyloxiran-2-yl]propyl]amino]-5-(2-methylpropoxy)azepane-1-carboxamide
  参考文献：
  名称：

  Design, synthesis, and evaluation of azepine-based cryptophycin mimetics

  摘要：

  Cryptophycins, depsipeptides isolated from terrestrial blue-green algae, show potent activity against a variety of tumor cell lines. Given the potential of the cryptophycins for cancer therapy, we developed a new class of non-peptide peptidomimetic, designed to replace the 16-membered macrolide ring with a 7-membered azepine ring for attachment of the cryptophycin side chains with the required spatial orientation to mimic the conformation of the relevant region of the natural product. Monte Carlo conformational analysis revealed excellent overlay of the local minimum structural model 6 and X-ray structure of (+)-cryptophycin-3 (5). Starting from this structural model, we designed and synthesized compounds (+)-25, (+)-30, and (+)-34 as potential mimics of cryptophycins. Compounds (+)-25, (+)-30, and (+)-34 were tested for in vitro cytotoxicity against six human cancer cell lines. Although only modest activities were observed, these results suggested that a new series of bioactive cryptophycin analogues might be available by structural modification of the central ring system of the cryptophycins. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(03)00857-3
• 作为产物：
  描述：

  N-苄基-N-(3-丁烯基)-3-丁烯基-1-胺 在 palladium on activated charcoal 、 Grubbs catalyst first generation 、 (S,S)-Jacobsen Cr(salen) catalyst 吡啶 、 正丁基锂 、 叠氮基三甲基硅烷 、 4 A molecular sieve 、 四丁基氟化铵 、 氢气 、 sodium hydride 、 sodium cyanoborohydride 、 戴斯-马丁氧化剂 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 溶剂黄146 、 苯 为溶剂， 反应 275.17h， 生成 (4R,5R)-N-[(4-methoxyphenyl)methyl]-4-[methyl-[(E,2R)-2-methyl-4-phenylbut-3-enyl]amino]-5-(2-methylpropoxy)azepane-1-carboxamide
  参考文献：
  名称：

  First Generation Design, Synthesis, and Evaluation of Azepine-Based Cryptophycin Analogues

  摘要：

  [GRAPHICS]Azepine-based cryptophycin mimics (+)-4 and (+)-5 have been designed and synthesized. Biological evaluation revealed modest in vitro activity against several human tumor cell lines, thereby supporting the utility of novel scaffolds for the design and:synthesis of cryptophycin analogues.

  DOI：

  10.1021/ol016799g

文献信息

• First Generation Design, Synthesis, and Evaluation of Azepine-Based Cryptophycin Analogues
  作者：Amos B. Smith、Young Shin Cho、Lisa E. Zawacki、Ralph Hirschmann、George R. Pettit

  DOI：10.1021/ol016799g

  日期：2001.12.1

  [GRAPHICS]Azepine-based cryptophycin mimics (+)-4 and (+)-5 have been designed and synthesized. Biological evaluation revealed modest in vitro activity against several human tumor cell lines, thereby supporting the utility of novel scaffolds for the design and:synthesis of cryptophycin analogues.
• Design, synthesis, and evaluation of azepine-based cryptophycin mimetics
  作者：Amos B Smith、Young Shin Cho、G.Robert Pettit、Ralph Hirschmann

  DOI：10.1016/s0040-4020(03)00857-3

  日期：2003.8

  Cryptophycins, depsipeptides isolated from terrestrial blue-green algae, show potent activity against a variety of tumor cell lines. Given the potential of the cryptophycins for cancer therapy, we developed a new class of non-peptide peptidomimetic, designed to replace the 16-membered macrolide ring with a 7-membered azepine ring for attachment of the cryptophycin side chains with the required spatial orientation to mimic the conformation of the relevant region of the natural product. Monte Carlo conformational analysis revealed excellent overlay of the local minimum structural model 6 and X-ray structure of (+)-cryptophycin-3 (5). Starting from this structural model, we designed and synthesized compounds (+)-25, (+)-30, and (+)-34 as potential mimics of cryptophycins. Compounds (+)-25, (+)-30, and (+)-34 were tested for in vitro cytotoxicity against six human cancer cell lines. Although only modest activities were observed, these results suggested that a new series of bioactive cryptophycin analogues might be available by structural modification of the central ring system of the cryptophycins. (C) 2003 Elsevier Ltd. All rights reserved.