8-(N,N-diacetylamino)-1',2-diacetyl-6-(4-methoxybenzyl)-2H-spiro[[1,2,4]triazolo [4,3-b][1,2,4]triazine-3,3'-indoline]-2',7(8H)-dione | 1373440-36-8

• 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: 8-(N,N-diacetylamino)-1',2-diacetyl-6-(4-methoxybenzyl)-2H-spiro[[1,2,4]triazolo [4,3-b][1,2,4]triazine-3,3'-indoline]-2',7(8H)-dione
• 英文别名: N-acetyl-N-[1',2-diacetyl-6-[(4-methoxyphenyl)methyl]-2',7-dioxospiro[[1,2,4]triazolo[4,3-b][1,2,4]triazine-3,3'-indole]-8-yl]acetamide
• CAS: 1373440-36-8
• 化学式: C₂₇H₂₅N₇O₇
• 分子量: 559.538
• InChiKey: ZVINHJIRTCEJDM-UHFFFAOYSA-N

物化性质

• 沸点：
  755.3±70.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  41
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  153
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  8-(N,N-diacetylamino)-1',2-diacetyl-6-(4-methoxybenzyl)-2H-spiro[[1,2,4]triazolo [4,3-b][1,2,4]triazine-3,3'-indoline]-2',7(8H)-dione 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 反应 2.0h， 生成
  参考文献：
  名称：

  Synthesis and evaluation of disulfide bond mimetics of amylin-(1–8) as agents to treat osteoporosis

  摘要：

  Osteoporotic fracture is a significant public health problem, resulting in fractures in >50% of women and in almost one third of men age 65 and older. Most of the existing therapies act by slowing bone loss, through inhibiting the action of bone resorbing cells. However, more substantial reductions of fracture numbers will only result from treatments that can rebuild bone. Our own animal studies demonstrated the anabolic potential of the small but unstable octapeptide fragment of amylin-(1-37), namely amylin-(1-8) containing one disulfide bridge (Cys/2 and Cys/7) [Am. J. Physiol. Endocrinol. Metab. 2000, 279, E730]. Herein, we describe the synthesis of amylin-(1-8) octapeptide and seven analogues thereof wherein the disulfide bridge is modified either via insertion of different linkers or bridges of a different nature in order to improve the stability and/or bone anabolic activity of the parent peptide. The peptide analogues were screened for proliferative activity in primary foetal rat bone-forming cells or osteoblasts at physiological concentrations. One such analogue showed promising biological activity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.02.030
• 作为产物：
  描述：

  4-amino-6-(4-methoxybenzyl)-3-hydrazino-4,5-dihydro-1,2,4-triazin-5-one 以 甲醇 为溶剂， 反应 12.0h， 生成 8-(N,N-diacetylamino)-1',2-diacetyl-6-(4-methoxybenzyl)-2H-spiro[[1,2,4]triazolo [4,3-b][1,2,4]triazine-3,3'-indoline]-2',7(8H)-dione
  参考文献：
  名称：

  新型稠合的1,2,4-三嗪衍生物作为强效CYP1A1活性抑制剂的合成与结构解析

  摘要：

  介绍了新系列的新型1,2,4-三嗪稠合衍生物3a – 3f，4a – 4i和6a – 6b的合成和结构解析及其抑制活性。通过1 H NMR，13 C NMR，MS光谱和元素分析确认了合成化合物的分子结构。对2-乙酰基-8-（N，N-二乙酰氨基）-6-（4-甲氧基苄基）-3-（4-甲氧基-苯基）-7-氧代-2,3-二氢- 7 H- [1,2,4]三唑[4,3- b ] [1,2,4]三嗪3d和2-乙酰基-8-（N-乙酰氨基）-6-苄基-3-（4-氯苯基）-3-甲基-7-氧代-2,3-二氢-7 H- [1,2,4]三唑[4,3- b ] [1 ，2,4]三嗪4e固定其结构。筛选了这些化合物对CPY1A1活性的抑制作用，以确定它们作为有前途的抗癌药物的潜力。我们的数据表明化合物4e，5a，5b和6b在所有测试化合物中具有最高的抑制作用。此外，对三唑三嗪衍生物对接的分析表明，这些化合物仅在蛋白质外

  DOI：

  10.1016/j.bmc.2012.02.041

文献信息

• Synthesis and structure elucidation of novel fused 1,2,4-triazine derivatives as potent inhibitors targeting CYP1A1 activity
  作者：Abdel Moneim EL Massry、Ahmed Mosaad Asal、Sherine Nabil Khattab、Nesreen Saied Haiba、Hala A. Awney、Mohamed Helmy、Vratislav Langer、Adel Amer

  DOI：10.1016/j.bmc.2012.02.041

  日期：2012.4

  l)-7-oxo-2,3-dihydro-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazine 3d and 2-acetyl-8-(N-acetylamino)-6-benzyl-3-(4-chlorophenyl)-3-methyl-7-oxo-2,3-dihydro-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazine 4e to secure their structures. The inhibitory effect of these compounds toward the CPY1A1 activity was screened to determine their potential as promising anticancer drugs. Our data showed that compounds 4e, 5a

  介绍了新系列的新型1,2,4-三嗪稠合衍生物3a – 3f，4a – 4i和6a – 6b的合成和结构解析及其抑制活性。通过1 H NMR，13 C NMR，MS光谱和元素分析确认了合成化合物的分子结构。对2-乙酰基-8-（N，N-二乙酰氨基）-6-（4-甲氧基苄基）-3-（4-甲氧基-苯基）-7-氧代-2,3-二氢- 7 H- [1,2,4]三唑[4,3- b ] [1,2,4]三嗪3d和2-乙酰基-8-（N-乙酰氨基）-6-苄基-3-（4-氯苯基）-3-甲基-7-氧代-2,3-二氢-7 H- [1,2,4]三唑[4,3- b ] [1 ，2,4]三嗪4e固定其结构。筛选了这些化合物对CPY1A1活性的抑制作用，以确定它们作为有前途的抗癌药物的潜力。我们的数据表明化合物4e，5a，5b和6b在所有测试化合物中具有最高的抑制作用。此外，对三唑三嗪衍生物对接的分析表明，这些化合物仅在蛋白质外
• Synthesis and evaluation of disulfide bond mimetics of amylin-(1–8) as agents to treat osteoporosis
  作者：Renata Kowalczyk、Paul W.R. Harris、Margaret A. Brimble、Karen E. Callon、Maureen Watson、Jillian Cornish

  DOI：10.1016/j.bmc.2012.02.030

  日期：2012.4

  Osteoporotic fracture is a significant public health problem, resulting in fractures in >50% of women and in almost one third of men age 65 and older. Most of the existing therapies act by slowing bone loss, through inhibiting the action of bone resorbing cells. However, more substantial reductions of fracture numbers will only result from treatments that can rebuild bone. Our own animal studies demonstrated the anabolic potential of the small but unstable octapeptide fragment of amylin-(1-37), namely amylin-(1-8) containing one disulfide bridge (Cys/2 and Cys/7) [Am. J. Physiol. Endocrinol. Metab. 2000, 279, E730]. Herein, we describe the synthesis of amylin-(1-8) octapeptide and seven analogues thereof wherein the disulfide bridge is modified either via insertion of different linkers or bridges of a different nature in order to improve the stability and/or bone anabolic activity of the parent peptide. The peptide analogues were screened for proliferative activity in primary foetal rat bone-forming cells or osteoblasts at physiological concentrations. One such analogue showed promising biological activity. (C) 2012 Elsevier Ltd. All rights reserved.