(2,5-dioxopyrrolidin-1-yl) 1H-imidazole-5-carboxylate | 885334-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (2,5-dioxopyrrolidin-1-yl) 1H-imidazole-5-carboxylate
• CAS: 885334-60-1
• 化学式: C₈H₇N₃O₄
• 分子量: 209.161
• InChiKey: WZIWEVGAEUPVFC-UHFFFAOYSA-N

物化性质

• 熔点：
  188-190 °C
• 沸点：
  472.4±37.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2,5-dioxopyrrolidin-1-yl) 1H-imidazole-5-carboxylate 、 1,7-二氨基庚烷 以 四氢呋喃 为溶剂， 以33%的产率得到
  参考文献：
  名称：

  Bis-imidazoles as molecular probes for peripheral sites of the zinc endopeptidase of botulinum neurotoxin serotype A

  摘要：

  Botulinum neurotoxin serotype A (BoNTA) is highly toxic, and its antidote is currently unavailable. The essential light-chain subunit of BoNTA is a zinc endopeptidase that can be used as a target for developing antidotes. However, the development of high-affinity, small-molecule inhibitors of the endopeptidase is as challenging as the development of small-molecule inhibitors of protein-protein complexation. This is because the polypeptide substrate wraps around the circumference of the endopeptidase upon binding, thereby constituting an unusually large substrate-enzyme interface of 4840 angstrom(2). To overcome the large-interface problem, we propose using the zinc-coordination and bivalence approaches to design inhibitors of BoNTA. Here we report the development of alkylene-linked bis-imidazoles that inhibit the endopeptidase in a two-site binding mode, The bis-imidazole tethered with 13 methylene groups, the most potent of the alkylene-linked dimers, showed 61% inhibition of the zinc endopeptidase of BoNTA at a concentration of 100 mu M. The results demonstrate the presence of a peripheral binding site for an imidazolium group at the rim of the BoNTA active-site cleft. This peripheral site enables the use of the bivalence approach to improve Our previously reported small-molecule inhibitors that were developed according to the zinc-coordination approach. (c) 2006 Elsevier Ltd All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.015
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 1H-咪唑-4-甲酸 在 N-甲基吗啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以83%的产率得到(2,5-dioxopyrrolidin-1-yl) 1H-imidazole-5-carboxylate
  参考文献：
  名称：

  Bis-imidazoles as molecular probes for peripheral sites of the zinc endopeptidase of botulinum neurotoxin serotype A

  摘要：

  Botulinum neurotoxin serotype A (BoNTA) is highly toxic, and its antidote is currently unavailable. The essential light-chain subunit of BoNTA is a zinc endopeptidase that can be used as a target for developing antidotes. However, the development of high-affinity, small-molecule inhibitors of the endopeptidase is as challenging as the development of small-molecule inhibitors of protein-protein complexation. This is because the polypeptide substrate wraps around the circumference of the endopeptidase upon binding, thereby constituting an unusually large substrate-enzyme interface of 4840 angstrom(2). To overcome the large-interface problem, we propose using the zinc-coordination and bivalence approaches to design inhibitors of BoNTA. Here we report the development of alkylene-linked bis-imidazoles that inhibit the endopeptidase in a two-site binding mode, The bis-imidazole tethered with 13 methylene groups, the most potent of the alkylene-linked dimers, showed 61% inhibition of the zinc endopeptidase of BoNTA at a concentration of 100 mu M. The results demonstrate the presence of a peripheral binding site for an imidazolium group at the rim of the BoNTA active-site cleft. This peripheral site enables the use of the bivalence approach to improve Our previously reported small-molecule inhibitors that were developed according to the zinc-coordination approach. (c) 2006 Elsevier Ltd All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.015

文献信息

• Bec, Christine Le; Roux, Pascal; Buc, Henri, Nucleosides and Nucleotides, 1997, vol. 16, # 7-9, p. 1301 - 1302
  作者：Bec, Christine Le、Roux, Pascal、Buc, Henri、Pochet, Sylvie

  DOI：——

  日期：——
• Bis-imidazoles as molecular probes for peripheral sites of the zinc endopeptidase of botulinum neurotoxin serotype A
  作者：Isidro Merino、Jason D. Thompson、Charles B. Millard、James J. Schmidt、Yuan-Ping Pang

  DOI：10.1016/j.bmc.2006.01.015

  日期：2006.5

  Botulinum neurotoxin serotype A (BoNTA) is highly toxic, and its antidote is currently unavailable. The essential light-chain subunit of BoNTA is a zinc endopeptidase that can be used as a target for developing antidotes. However, the development of high-affinity, small-molecule inhibitors of the endopeptidase is as challenging as the development of small-molecule inhibitors of protein-protein complexation. This is because the polypeptide substrate wraps around the circumference of the endopeptidase upon binding, thereby constituting an unusually large substrate-enzyme interface of 4840 angstrom(2). To overcome the large-interface problem, we propose using the zinc-coordination and bivalence approaches to design inhibitors of BoNTA. Here we report the development of alkylene-linked bis-imidazoles that inhibit the endopeptidase in a two-site binding mode, The bis-imidazole tethered with 13 methylene groups, the most potent of the alkylene-linked dimers, showed 61% inhibition of the zinc endopeptidase of BoNTA at a concentration of 100 mu M. The results demonstrate the presence of a peripheral binding site for an imidazolium group at the rim of the BoNTA active-site cleft. This peripheral site enables the use of the bivalence approach to improve Our previously reported small-molecule inhibitors that were developed according to the zinc-coordination approach. (c) 2006 Elsevier Ltd All rights reserved.