N-benzyloxycarbonyl-N'-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide | 213554-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: N-benzyloxycarbonyl-N'-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide
• 英文别名: 5'-deoxy-2',3'-O-(1-methylethylidene)-adenosine 5'-N-[(phenylmethoxy)carbonyl]-sulfamide；benzyl N-[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methylsulfamoyl]carbamate
• CAS: 213554-34-8
• 化学式: C₂₁H₂₅N₇O₇S
• 分子量: 519.538
• InChiKey: GHIKPBPKIZZNAM-NVQRDWNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  190
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N-benzyloxycarbonyl-N'-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide 在 甲酸 、 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 水 、 乙腈 为溶剂， 反应 31.5h， 生成 N-cinnamoyl-N'-(5'-deoxyadenosin-5'-yl)sulfamide
  参考文献：
  名称：

  Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors

  摘要：

  4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-coumaric, caffeic, and ferulic acids, and the regulatory position of 4CL in the phenylpropanoid pathway renders the enzyme an attractive target that controls the composition of phenylpropanoids in plants. In this study, we designed and synthesized mechanism- based inhibitors for 4CL in order to develop useful tools for the investigation of physiological functions of 4CL and chemical agents that modulate plant growth with the ultimate goal to produce plant biomass that exhibits features that are beneficial to humans. The acylsulfamide backbone of the inhibitors in this study was adopted as a mimic of the acyladenylate intermediates in the catalytic reaction of 4CL. These acylsulfamide inhibitors and the important synthetic intermediates were fully characterized using two-dimensional NMR spectroscopy. Five 4CL proteins with distinct substrate specificity from four plant species, i.e., Arabidopsis thaliana, Glycine max (soybean), Populus trichocarpa (poplar), and Petunia hybrida (petunia), were used to evaluate the inhibitory activity, and the half-maximum inhibitory concentration (IC50) of each acylsulfamide in the presence of 4-coumaric acid (100 mu M) was determined as an index of inhibitory activity. The synthetic acylsulfamides used in this study inhibited the 4CLs with IC50 values ranging from 0.10 to 722 mM, and the IC50 values of the most potent inhibitors for each 4CL were 0.10-2.4 mM. The structure-activity relationship observed in this study revealed that both the presence and the structure of the acyl group of the synthetic inhibitors strongly affect the inhibitory activity, and indicates that 4CL recognizes the acylsulfamide inhibitors as acyladenylate mimics. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.04.006
• 作为产物：
  描述：

  氯磺酰异氰酸酯 、 5-氨基-5-脱氧-2,3-O-(1-甲基亚乙基)-腺苷酸 、 苯甲醇 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以82%的产率得到N-benzyloxycarbonyl-N'-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide
  参考文献：
  名称：

  Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors

  摘要：

  4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-coumaric, caffeic, and ferulic acids, and the regulatory position of 4CL in the phenylpropanoid pathway renders the enzyme an attractive target that controls the composition of phenylpropanoids in plants. In this study, we designed and synthesized mechanism- based inhibitors for 4CL in order to develop useful tools for the investigation of physiological functions of 4CL and chemical agents that modulate plant growth with the ultimate goal to produce plant biomass that exhibits features that are beneficial to humans. The acylsulfamide backbone of the inhibitors in this study was adopted as a mimic of the acyladenylate intermediates in the catalytic reaction of 4CL. These acylsulfamide inhibitors and the important synthetic intermediates were fully characterized using two-dimensional NMR spectroscopy. Five 4CL proteins with distinct substrate specificity from four plant species, i.e., Arabidopsis thaliana, Glycine max (soybean), Populus trichocarpa (poplar), and Petunia hybrida (petunia), were used to evaluate the inhibitory activity, and the half-maximum inhibitory concentration (IC50) of each acylsulfamide in the presence of 4-coumaric acid (100 mu M) was determined as an index of inhibitory activity. The synthetic acylsulfamides used in this study inhibited the 4CLs with IC50 values ranging from 0.10 to 722 mM, and the IC50 values of the most potent inhibitors for each 4CL were 0.10-2.4 mM. The structure-activity relationship observed in this study revealed that both the presence and the structure of the acyl group of the synthetic inhibitors strongly affect the inhibitory activity, and indicates that 4CL recognizes the acylsulfamide inhibitors as acyladenylate mimics. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.04.006

文献信息

• Aminoacyl sulfamides for the treatment of hyperproliferative disorders
  申请人：Cubist Pharmaceuticals, Inc.

  公开号：US05824657A1

  公开（公告）日：1998-10-20

  Novel aminoacyl sulfamides are described. These compounds are effective in the treatment of hyperproliferative disorders, specifically psoriasis. Exemplary compounds of this invention are 5'-deoxy-adenosine 5'-N(N-L-phenylalanyl)sulfamide and 5'-deoxy-adenosine 5'-N-(N-L-tryptophanyl)sulfamide.

  小说氨酰磺胺已被描述。这些化合物在治疗过度增殖性疾病，特别是牛皮癣方面非常有效。本发明的示范化合物包括5'-去氧腺苷5'-N(N-L-苯丙氨酰)磺胺和5'-去氧腺苷5'-N-(N-L-色氨酰)磺胺。
• AMINOACYL SULFAMIDES FOR THE TREATMENT OF HYPERPROLIFERATIVE DISORDERS
  申请人：Cubist Pharmaceuticals, Inc.

  公开号：EP0991412B1

  公开（公告）日：2003-03-12
• US5824657A
  申请人：——

  公开号：US5824657A

  公开（公告）日：1998-10-20
• Synthesis and inhibitory activity of mechanism-based 4-coumaroyl-CoA ligase inhibitors
  作者：Bunta Watanabe、Hiroaki Kirikae、Takao Koeduka、Yoshinori Takeuchi、Tomoki Asai、Yoshiyuki Naito、Hideya Tokuoka、Shinri Horoiwa、Yoshiaki Nakagawa、Bun-ichi Shimizu、Masaharu Mizutani、Jun Hiratake

  DOI：10.1016/j.bmc.2018.04.006

  日期：2018.5

  4-Coumaroyl-CoA ligase (4CL) is ubiquitous in the plant kingdom, and plays a central role in the biosynthesis of phenylpropanoids such as lignins, flavonoids, and coumarins. 4CL catalyzes the formation of the coenzyme A thioester of cinnamates such as 4-coumaric, caffeic, and ferulic acids, and the regulatory position of 4CL in the phenylpropanoid pathway renders the enzyme an attractive target that controls the composition of phenylpropanoids in plants. In this study, we designed and synthesized mechanism- based inhibitors for 4CL in order to develop useful tools for the investigation of physiological functions of 4CL and chemical agents that modulate plant growth with the ultimate goal to produce plant biomass that exhibits features that are beneficial to humans. The acylsulfamide backbone of the inhibitors in this study was adopted as a mimic of the acyladenylate intermediates in the catalytic reaction of 4CL. These acylsulfamide inhibitors and the important synthetic intermediates were fully characterized using two-dimensional NMR spectroscopy. Five 4CL proteins with distinct substrate specificity from four plant species, i.e., Arabidopsis thaliana, Glycine max (soybean), Populus trichocarpa (poplar), and Petunia hybrida (petunia), were used to evaluate the inhibitory activity, and the half-maximum inhibitory concentration (IC50) of each acylsulfamide in the presence of 4-coumaric acid (100 mu M) was determined as an index of inhibitory activity. The synthetic acylsulfamides used in this study inhibited the 4CLs with IC50 values ranging from 0.10 to 722 mM, and the IC50 values of the most potent inhibitors for each 4CL were 0.10-2.4 mM. The structure-activity relationship observed in this study revealed that both the presence and the structure of the acyl group of the synthetic inhibitors strongly affect the inhibitory activity, and indicates that 4CL recognizes the acylsulfamide inhibitors as acyladenylate mimics. (C) 2018 Elsevier Ltd. All rights reserved.