1-[(aminosulfonyl)amino]-1-deoxy-2,3:4,5-bis-O-(isopropylidene)-D-fructopyranose | 205248-69-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧吡喃
• 英文名称: 1-[(aminosulfonyl)amino]-1-deoxy-2,3:4,5-bis-O-(isopropylidene)-D-fructopyranose
• 英文别名: N-{[(3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxolo[4,5-b:4',5'-d]pyran-3a-yl]methyl}sulfamide；(1R,2S,6S,9R)-4,4,11,11-tetramethyl-6-[(sulfamoylamino)methyl]-3,5,7,10,12-pentaoxatricyclo[7.3.0.02,6]dodecane
• CAS: 205248-69-7
• 化学式: C₁₂H₂₂N₂O₇S
• 分子量: 338.382
• InChiKey: NQRKKQKMTGLNOZ-XBWDGYHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-[(aminosulfonyl)amino]-1-deoxy-2,3:4,5-bis-O-(isopropylidene)-D-fructopyranose 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以2.40 g的产率得到
  参考文献：
  名称：

  碳酸酐酶-II抑制作用。托吡酯的磺酰胺同源物的真正的酶抑制特性是什么？

  摘要：

  市售的药物托吡酯（1）是中等程度的碳酸酐酶II（CA-II）抑制剂（K i或K d = 0.3-0.6 microM），而磺酰胺co酸酯2是相对较弱的抑制剂（K i或K d = 25-650 microM）。Winum等人从2.CA-II的X射线共晶体结构中得出。（J. Med。Chem。2006，49，7024）提出2的C8甲基与CA-II的Ala-65之间不利的空间相互作用是造成CA-II抑制力2降低的原因。通过合成和检查配体3来直接测试Ala-65的这种作用，该配体3中缺少令人讨厌的（pro-S或C8）甲基取代基。我们还制备并评估了相关的磺酰胺5、7和9。在CA-II中抑制试验（4-硝基苯乙酸乙酸酯），对3的K i约为300 microM，表明抑制作用非常弱，接近对2的抑制作用（4NPA，K i = 340 microM）。在CA-II结合测定（ThermoFluor）中，3的K d>

  DOI：

  10.1021/jm7015649
• 作为产物：
  描述：

  1-azido-1-deoxy-2,3:4,5-di-O-isopropylidene-β-D-fructopyranose 在 palladium on activated charcoal 氢气 、 磺酰胺 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 23.0 ℃ 、324.05 kPa 条件下， 反应 26.0h， 生成 1-[(aminosulfonyl)amino]-1-deoxy-2,3:4,5-bis-O-(isopropylidene)-D-fructopyranose
  参考文献：
  名称：

  Comparison of Sulfamate and Sulfamide Groups for the Inhibition of Carbonic Anhydrase-II by Using Topiramate as a Structural Platform

  摘要：

  This paper examines the relative effectiveness of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II (CA-H). Topiramate (1) and its sulfamide analogue 4, and 4,5-cyclic sulfate 6 and its sulfamide analogue 5, were compared for inhibition of human CA-II. A colorimetric assay, based on the pH shift that accompanies hydration of carbon dioxide, and an esterase assay were used. For these bioisosteric pairs, 1/4 and 6/5, the sulfamate compound was markedly more potent than its sulfamide counterpart. A similar, large difference in potency was also observed for the sulfamate/sulfamide pairs 14/15 and 16/17. These results indicate that the sulfamide moiety is not particularly suitable for obtaining potent carbonic anhydrase inhibition. A discussion of this structure-activity relationship with respect to the interactions of 1 and 6 with CA-H from published X-ray data is presented. A metabolic acidosis study was performed in rats with 1, 4, 6, and 2, and the results are discussed with respect to the degree of inhibition of CA-II in vivo.

  DOI：

  10.1021/jm040124c

文献信息

• Structure−Activity Studies on Anticonvulsant Sugar Sulfamates Related to Topiramate. Enhanced Potency with Cyclic Sulfate Derivatives
  作者：Bruce E. Maryanoff、Michael J. Costanzo、Samuel O. Nortey、Michael N. Greco、Richard P. Shank、James J. Schupsky、Marta P. Ortegon、Jeffry L. Vaught

  DOI：10.1021/jm970790w

  日期：1998.4.1

  22-25, 27, 84), (2) the linker between the sulfamate group and the pyran ring (9, 10, 21a,b), (3) the substituents on the 2,3- (58-60, 85, 86) and 4, 5-fused (30-38, 43, 45-47, 52, 53) 1,3-dioxolane rings, (4) the constitution of the 4,5-fused 1,3-dioxolane ring (2, 54, 55, 63-68, 76, 77, 80, 83a-r, 84-87, 90a, 91a, 93a), (5) the ring oxygen atoms (95, 96, 100-102, 104, 105), and (6) the absolute stereochemistry

  我们已经探索了围绕临床有效的抗癫痫药托吡酯（1）的结构-活性关系（SAR），这是在我们的实验室中发现的一种独特的糖氨基磺酸盐类抗惊厥药。母体化合物的系统结构修饰旨在鉴定具有长效作用时间和良好神经毒性指数的有效抗惊厥药。在此背景下，我们探讨了几种分子特征的药理重要性：（1）氨基磺酸酯基团（6-8、22-25、27、84），（2）氨基磺酸酯基团与吡喃环之间的连接子（9） ，10、21a，b），（3）2,3-（58-60、85、86）和4,5-稠合（30-38、43、45-47、52、53）1上的取代基，3-二氧戊环，（4）4,5-稠合的1,3-二氧戊环的结构（2，54，55，63-68，76，77，80，83a-r，84-87，90a ，91a，93a），（5）环氧原子（95、96、100-102、104、105），和（6）绝对立体化学（106和107）。通过对氨基磺酸氨基甲酸酯21a的主要非
• Process for preparation of sulfamide derivatives
  申请人：Abdel-Magid F. Ahmed

  公开号：US20060270856A1

  公开（公告）日：2006-11-30

  The present invention is directed to novel process for the preparation of sulfonylimine and sulfamide derivatives.

  本发明涉及一种新型用于制备磺酰亚胺和磺酰胺衍生物的方法。
• US8283478B2
  申请人：——

  公开号：US8283478B2

  公开（公告）日：2012-10-09
• Comparison of Sulfamate and Sulfamide Groups for the Inhibition of Carbonic Anhydrase-II by Using Topiramate as a Structural Platform
  作者：Bruce E. Maryanoff、David F. McComsey、Michael J. Costanzo、Coralie Hochman、Virginia Smith-Swintosky、Richard P. Shank

  DOI：10.1021/jm040124c

  日期：2005.3.1

  This paper examines the relative effectiveness of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II (CA-H). Topiramate (1) and its sulfamide analogue 4, and 4,5-cyclic sulfate 6 and its sulfamide analogue 5, were compared for inhibition of human CA-II. A colorimetric assay, based on the pH shift that accompanies hydration of carbon dioxide, and an esterase assay were used. For these bioisosteric pairs, 1/4 and 6/5, the sulfamate compound was markedly more potent than its sulfamide counterpart. A similar, large difference in potency was also observed for the sulfamate/sulfamide pairs 14/15 and 16/17. These results indicate that the sulfamide moiety is not particularly suitable for obtaining potent carbonic anhydrase inhibition. A discussion of this structure-activity relationship with respect to the interactions of 1 and 6 with CA-H from published X-ray data is presented. A metabolic acidosis study was performed in rats with 1, 4, 6, and 2, and the results are discussed with respect to the degree of inhibition of CA-II in vivo.
• Carbonic Anhydrase-II Inhibition. What are the True Enzyme–Inhibitory Properties of the Sulfamide Cognate of Topiramate?
  作者：Bruce E. Maryanoff、David F. McComsey、Jung Lee、Virginia L. Smith-Swintosky、Yuanping Wang、Lisa K. Minor、Matthew J. Todd

  DOI：10.1021/jm7015649

  日期：2008.4.1

  The marketed drug topiramate ( 1) is a moderate inhibitor of carbonic anhydrase-II (CA-II) ( K i or K d = 0.3-0.6 microM), whereas sulfamide cognate 2 is a comparatively weak inhibitor ( K i or K d = 25-650 microM). From an X-ray cocrystal structure of 2.CA-II, Winum et al. ( J. Med. Chem. 2006, 49, 7024) proposed that an adverse steric interaction between the C8 methyl group in 2 and Ala-65 of CA-II

  市售的药物托吡酯（1）是中等程度的碳酸酐酶II（CA-II）抑制剂（K i或K d = 0.3-0.6 microM），而磺酰胺co酸酯2是相对较弱的抑制剂（K i或K d = 25-650 microM）。Winum等人从2.CA-II的X射线共晶体结构中得出。（J. Med。Chem。2006，49，7024）提出2的C8甲基与CA-II的Ala-65之间不利的空间相互作用是造成CA-II抑制力2降低的原因。通过合成和检查配体3来直接测试Ala-65的这种作用，该配体3中缺少令人讨厌的（pro-S或C8）甲基取代基。我们还制备并评估了相关的磺酰胺5、7和9。在CA-II中抑制试验（4-硝基苯乙酸乙酸酯），对3的K i约为300 microM，表明抑制作用非常弱，接近对2的抑制作用（4NPA，K i = 340 microM）。在CA-II结合测定（ThermoFluor）中，3的K d>