N-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide | 29144-95-4

• 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-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide
• 英文别名: 5’-deoxy-2',3'-O-isopropylidene-5'-N-(sulfamoyl)aminoadenosine；5'-[N-sulfamoyl]amino-2',3'-O-isopropylidene-5'-deoxyadenosine；9-[(3aS,4R,6R)-2,2-dimethyl-6-[(sulfamoylamino)methyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-aminopurine；2',3'-O-Isopropyliden-5'-N-sulfamoylamino-5'-deoxyadenosin；O^2'_,O3'-isopropylidene-5'-sulfamoylamino-5'-deoxy-adenosine；9-[(3aR,4R,6R,6aR)-2,2-dimethyl-6-[(sulfamoylamino)methyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-aminopurine
• CAS: 29144-95-4
• 化学式: C₁₃H₁₉N₇O₅S
• 分子量: 385.404
• InChiKey: SQLNOXBXZXUJGZ-WOUKDFQISA-N

物化性质

• 沸点：
  679.1±65.0 °C(Predicted)
• 密度：
  1.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.38
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  169.5
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide 在 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  [EN] SULFANIDE ADENOSINE DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS D'ADÉNOSINE SULFANIDE ET LEURS UTILISATIONS

  摘要：

  本文描述了化合物的磺胺基腺苷衍生物，其化学式为(I)或(II)，以及其药学上可接受的盐和药物组合物。还提供了涉及创新化合物或药物组合物用于治疗和/或预防增殖性疾病（例如癌症、炎症性疾病和自身免疫疾病）或传染性疾病（例如细菌感染、病毒感染、真菌感染和寄生虫病）的方法、用途和试剂盒。据认为，本文描述的化合物和药物组合物能够通过抑制生物样本或受试者中的氨酰tRNA合成酶活性来实现治疗增殖性疾病或传染性疾病。

  公开号：

  WO2016201374A1
• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 偶氮二甲酸二异丙酯 、 N-(苄氧基羰基)磺酰氯 、 三乙胺 、 三苯基膦 、 肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 N-(2',3'-O-isopropylidene-5'-deoxyadenosin-5'-yl)sulfamide
  参考文献：
  名称：

  [EN] SULFANIDE ADENOSINE DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS D'ADÉNOSINE SULFANIDE ET LEURS UTILISATIONS

  摘要：

  本文描述了化合物的磺胺基腺苷衍生物，其化学式为(I)或(II)，以及其药学上可接受的盐和药物组合物。还提供了涉及创新化合物或药物组合物用于治疗和/或预防增殖性疾病（例如癌症、炎症性疾病和自身免疫疾病）或传染性疾病（例如细菌感染、病毒感染、真菌感染和寄生虫病）的方法、用途和试剂盒。据认为，本文描述的化合物和药物组合物能够通过抑制生物样本或受试者中的氨酰tRNA合成酶活性来实现治疗增殖性疾病或传染性疾病。

  公开号：

  WO2016201374A1

文献信息

• Development of small-molecule inhibitors of fatty acyl-AMP and fatty acyl-CoA ligases in Mycobacterium tuberculosis
  作者：Marzena Baran、Kimberly D. Grimes、Paul A. Sibbald、Peng Fu、Helena I.M. Boshoff、Daniel J. Wilson、Courtney C. Aldrich

  DOI：10.1016/j.ejmech.2020.112408

  日期：2020.9

  biochemical roles of many FACLs remain poorly characterized while the functionally non-redundant FAALs are much better understood. Here we describe the systematic investigation of 5′-O-[N-(alkanoyl)sulfamoyl]adenosine (alkanoyl adenosine monosulfamate, alkanoyl-AMS) analogs as potential multitarget FadD inhibitors for their antitubercular activity and biochemical selectivity towards representative FAAL and

  结核分枝杆菌( Mtb ) 的脂质代谢依赖 34 种脂肪酸腺苷酸化酶 (FAdDs)，可分为两类：参与脂质和胆固醇分解代谢的脂肪酰基辅酶 A 连接酶 (FACL) 和长链脂肪酰基-AMP 连接酶 (FAAL) ) 参与Mtb 中发现的许多必需和赋予毒力的脂质的生物合成。许多 FACL 的精确生化作用仍不清楚，而功能非冗余的 FAAL 则更好理解。这里，我们描述的5'-系统调查ö - [ ñ - （链烷酰基）氨磺酰基]腺苷（烷酰基一denosine米ONO小号ulFAa href=https://www.molaid.com/MS_77914 target="_blank">AMate, alkanoyl-AMS) 类似物作为潜在的多靶点 FAdD 抑制剂，因为它们具有抗结核活性和对代表性 FAAL 和 FACL 酶的生化选择性。我们鉴定了几种有效的化合物，包括 12-叠氮十二烷酰基-AMS 28、11-苯氧基十一烷酰基-AMS 32和壬氧基乙酰基-AMS 36，其对结核分枝杆菌的最小抑制浓度 (MIC)范围为
• Biosynthesis, Mechanism of Action, and Inhibition of the Enterotoxin Tilimycin Produced by the Opportunistic Pathogen <i>Klebsiella oxytoca</i>
  作者：Evan M. Alexander、Dale F. Kreitler、Valeria Guidolin、Alexander K. Hurben、Eric Drake、Peter W. Villalta、Silvia Balbo、Andrew M. Gulick、Courtney C. Aldrich

  DOI：10.1021/acsinfecdis.0c00326

  日期：2020.7.10

  Tilimycin is an enterotoxin produced by the opportunistic pathogen Klebsiella oxytoca that causes antibiotic-associated hemorrhagic colitis (AAHC). This pyrrolobenzodiazepine (PBD) natural product is synthesized by a bimodular nonribosomal peptide synthetase (NRPS) pathway composed of three proteins: NpsA, ThdA, and NpsB. We describe the functional and structural characterization of the fully reconstituted NRPS system and report the steady-state kinetic analysis of all natural substrates and cofactors as well as the structural characterization of both NpsA and ThdA. The mechanism of action of tilimycin was confirmed using DNA adductomics techniques through the detection of putative N-2 guanine alkylation after tilimycin exposure to eukaryotic cells, providing the first structural characterization of a PBD-DNA adduct formed in cells. Finally, we report the rational design of small-molecule inhibitors that block tilimycin biosynthesis in whole cell K. oxytoca (IC₅₀ = 29 ± 4 μM) through the inhibition of NpsA (K_D = 29 ± 4 nM).
• 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.
• [EN] FRET-BASED ASSAYS<br/>[FR] DOSAGES PAR FRET
  申请人：[en]THE GENERAL HOSPITAL CORPORATION

  公开号：WO2023004438A2

  公开（公告）日：2023-01-26

  The present application provides compounds and methods for identifying a modulator of a protein of interest using TR-FRET donor attached to the protein of interest and a tracer containing TR-FRET acceptor.