methyl (2S)-2-[[4-(dimethylamino)-6-[[[(1S)-1-(1H-imidazol-4-ylmethyl)-2-methoxy-2-oxo-ethyl]amino]methyl]-2-pyridyl]methylamino]-3-(1H-imidazol-4-yl)propanoate | 153503-99-2

• 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 (2S)-2-[[4-(dimethylamino)-6-[[[(1S)-1-(1H-imidazol-4-ylmethyl)-2-methoxy-2-oxo-ethyl]amino]methyl]-2-pyridyl]methylamino]-3-(1H-imidazol-4-yl)propanoate
• 英文别名: methyl (2S)-2-[[4-(dimethylamino)-6-[[[(2S)-3-(1H-imidazol-5-yl)-1-methoxy-1-oxopropan-2-yl]amino]methyl]pyridin-2-yl]methylamino]-3-(1H-imidazol-5-yl)propanoate
• CAS: 153503-99-2
• 化学式: C₂₃H₃₂N₈O₄
• 分子量: 484.558
• InChiKey: YVUROPAXIFKXPJ-SFTDATJTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  35
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[4-(dimethylamino)-6-[[[(1S)-1-(1H-imidazol-4-ylmethyl)-2-methoxy-2-oxo-ethyl]amino]methyl]-2-pyridyl]methylamino]-3-(1H-imidazol-4-yl)propanoate 在 吡啶 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 35.0h， 生成 4-(dimethylamino)-2,6-bis<<<(S)-1-carboxy-2-<(triphenylmethyl)imidazol-4-yl>ethyl>amino>methyl>pyridine
  参考文献：
  名称：

  新型锌螯合剂在抑制κB位点结合蛋白HIV-EP1和NF-κB中具有双重活性。

  摘要：

  锌指蛋白HIV-EP1（也称为PRDII-BF1或MBP-1）和Rel家族蛋白NF-kappa B都与存在于参与免疫的多个细胞和病毒基因的增强子中的kappa B位点结合功能和炎症反应，包括HIV-1 LTR和人类干扰素β基因。当细胞暴露于细胞外刺激物（如病毒或佛波酯）时，HIV-EP1和NF-κB的活性均被诱导。因此，κB定点转录可以由两种不同的蛋白质以协同方式调节。已经设计并合成了包含（二甲基氨基）吡啶和组氨酸单元即1-4的新型杂环化合物，旨在抑制这些κB位点结合蛋白以区别其功能。NMR研究表明，这些化合物具有出色的锌结合能力。化合物1和2通过去除锌而对HIV-EP1的DNA结合活性具有显着的抑制作用，而不会干扰NF-κB的DNA结合活性。由于已证明锌以某种方式影响NF-κ的DNA结合。 B，检查了这些杂环化合物及其锌络合物对NF-κB的影响。3和4的锌复合物对NF-κB的DNA结合和

  DOI：

  10.1021/jm00017a011
• 作为产物：
  描述：

  4-(dimethylamino)picolinaldehyde 在 盐酸 、 三氟化硼乙醚 、 水 、 三乙酰氧基硼氢化钠 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 102.5h， 生成 methyl (2S)-2-[[4-(dimethylamino)-6-[[[(1S)-1-(1H-imidazol-4-ylmethyl)-2-methoxy-2-oxo-ethyl]amino]methyl]-2-pyridyl]methylamino]-3-(1H-imidazol-4-yl)propanoate
  参考文献：
  名称：

  Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine–pyridine–histidine system

  摘要：

  Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251. HPH-1Trt and HPH-2Trt were highly active among the tested HPH compounds. In vitro DNA cleavage assay showed both HPH-1Trt and HPH-2Trt completely disintegrate pUC19 DNA. The introduction of trityl group decisively potentiated the activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.044

文献信息

• JP2016/160223
  申请人：——

  公开号：——

  公开（公告）日：——
• Restructuring of the bleomycin metal core. Novel oxygen-activating ligands with symmetrized structure
  作者：Masami Otsuka、Honoo Satake、Yukio Sugiura、Satoru Murakami、Masakatsu Shibasaki、Susumu Kobayashi

  DOI：10.1016/s0040-4039(00)61368-0

  日期：——

  Novel ligands having symmetrized coordination environment consisting of two histidine units and a pyridine are prepared. Oxygen activating efficiency of the iron complexes of the synthetic ligands increases by introducing electron donating substituent into the pyridine ring.
• Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine–pyridine–histidine system
  作者：Taha F.S. Ali、Kana Iwamaru、Halil Ibrahim Ciftci、Ryoko Koga、Masahiro Matsumoto、Yasunori Oba、Hiromasa Kurosaki、Mikako Fujita、Yoshinari Okamoto、Kazuo Umezawa、Mitsuyoshi Nakao、Takuichiro Hide、Keishi Makino、Jun-ichi Kuratsu、Mohamed Abdel-Aziz、Gamal El-Din A.A. Abuo-Rahma、Eman A.M. Beshr、Masami Otsuka

  DOI：10.1016/j.bmc.2015.07.044

  日期：2015.9

  Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251. HPH-1Trt and HPH-2Trt were highly active among the tested HPH compounds. In vitro DNA cleavage assay showed both HPH-1Trt and HPH-2Trt completely disintegrate pUC19 DNA. The introduction of trityl group decisively potentiated the activity. (C) 2015 Elsevier Ltd. All rights reserved.
• Novel Zinc Chelators with Dual Activity in the Inhibition of the .kappa.B Site-Binding Proteins, HIV-EP1 and NF-.kappa.B
  作者：Masami Otsuka、Mikako Fujita、Tsutomu Aoki、Shunsuke Ishii、Yukio Sugiura、Tadashi Yamamoto、Jun-ichiro Inoue

  DOI：10.1021/jm00017a011

  日期：1995.8

  effect on the DNA binding activity of HIV-EP1 by removing zinc without interfering with the DNA binding activity of NF-kappa B. Since it has been demonstrated that zinc somehow influences the DNA binding of NF-kappa B, the effect of these heterocyclic compounds and their zinc complexes on NF-kappa B was examined. Zinc complexes of 3 and 4 exhibited the inhibitory effect on the DNA binding of NF-kappa B

  锌指蛋白HIV-EP1（也称为PRDII-BF1或MBP-1）和Rel家族蛋白NF-kappa B都与存在于参与免疫的多个细胞和病毒基因的增强子中的kappa B位点结合功能和炎症反应，包括HIV-1 LTR和人类干扰素β基因。当细胞暴露于细胞外刺激物（如病毒或佛波酯）时，HIV-EP1和NF-κB的活性均被诱导。因此，κB定点转录可以由两种不同的蛋白质以协同方式调节。已经设计并合成了包含（二甲基氨基）吡啶和组氨酸单元即1-4的新型杂环化合物，旨在抑制这些κB位点结合蛋白以区别其功能。NMR研究表明，这些化合物具有出色的锌结合能力。化合物1和2通过去除锌而对HIV-EP1的DNA结合活性具有显着的抑制作用，而不会干扰NF-κB的DNA结合活性。由于已证明锌以某种方式影响NF-κ的DNA结合。 B，检查了这些杂环化合物及其锌络合物对NF-κB的影响。3和4的锌复合物对NF-κB的DNA结合和