2,3-O-(1-甲基亚乙基)-beta-D-吡喃果糖1-氨基磺酸酯 | 106881-41-8

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧吡喃
• 中文名称: 2,3-O-(1-甲基亚乙基)-beta-D-吡喃果糖1-氨基磺酸酯
• 中文别名: 3-吡唑烷酮,4,4-二乙基-1-甲基-；托吡酯4,5-去甲异亚丙基杂质
• 英文名称: 2,3-O-(1-Methylethylidene)-β-D-fructopyranose 1-sulfamate
• 英文别名: 2,3:-O-(1-methylethylidene)-β-D-fructo-pyranose sulfamate；2,3-O-(1-methylethylidene)-β-D-fructopyranose sulfamate；4,5-Desisopropylidene Topiramate；[(3aS,6R,7R,7aS)-6,7-dihydroxy-2,2-dimethyl-5,6,7,7a-tetrahydro-[1,3]dioxolo[4,5-b]pyran-3a-yl]methyl sulfamate
• CAS: 106881-41-8
• 化学式: C₉H₁₇NO₈S
• 分子量: 299.302
• InChiKey: CKFVNUZYZFRVCR-JAKMQLQISA-N

物化性质

• 熔点：
  >120°C (dec.)
• 沸点：
  503.3±60.0 °C(Predicted)
• 密度：
  1.549±0.06 g/cm3(Predicted)
• 溶解度：
  甲醇（微溶、超声处理）、水（微溶、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2,3-O-(1-甲基亚乙基)-beta-D-吡喃果糖1-氨基磺酸酯 在 吡啶 、 磺酰氯 作用下， 以 乙酸乙酯 为溶剂， 以100%的产率得到4,5-bis-O-chlorosulfonyl-2,3-O-(1-methylethylidene)-β-D-fructopyranose sulfamate
  参考文献：
  名称：

  与托吡酯有关的抗惊厥糖氨基磺酸盐的结构活性研究。环状硫酸盐衍生物的效力增强。

  摘要：

  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

  DOI：

  10.1021/jm970790w
• 作为产物：
  描述：

  托吡酯 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 以31%的产率得到2,3-O-(1-甲基亚乙基)-beta-D-吡喃果糖1-氨基磺酸酯
  参考文献：
  名称：

  抗惊厥性O-烷基氨基磺酸盐。2,3：4,5-双-O-（1-甲基亚乙基）-β-D-果糖基氨基磺酸氨基磺酸盐及相关化合物。

  摘要：

  已发现新型糖氨基磺酸盐1（McN-4853，托吡酯）具有类似于苯妥英的强效抗惊厥活性。在最大的电击惊厥试验中，在小鼠2小时口服时，1的ED50为39 mg / kg。口服1的作用持续时间超过8小时。讨论了1的药理学其他方面，以及神经化学和碳酸酐酶抑制作用。讨论了1在溶液和固态中的构象行为。合成了一系列类似的1，并检查了其抗惊厥性质。

  DOI：

  10.1021/jm00388a023

文献信息

• Anticonvulsant sorbopyranose sulfamates
  申请人：McNeilab, Inc.

  公开号：US05384327A1

  公开（公告）日：1995-01-24

  Sulfamate derivatives having the following formula (I): ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are as herein defined, have been found to exhibit anticonvulsant activity and are thus useful in the treatment of conditions such as epilepsy. Further, the present invention encompasses pharmaceutical compositions containing a compound of formula (I) as well as methods for their use and novel intermediates are disclosed.

  具有以下式子（I）的磺酰胺衍生物：##STR1## 其中R.sub.1，R.sub.2，R.sub.3，R.sub.4，R.sub.5和R.sub.6如所定义，已被发现具有抗惊厥活性，因此在治疗癫痫等疾病方面非常有用。此外，本发明还包括含有式（I）化合物的制药组合物，以及使用它们的方法和新的中间体。
• Anticonvulsant fructopyranose cyclic sulfites and sulfates
  申请人：MCNEILAB, INC.

  公开号：EP0568306A1

  公开（公告）日：1993-11-03

  Compounds of the general formula (I): wherein R₁, R₂, R₃, R₄, R₅, R₆, n and p are as herein defined; exhibit anticonvulsant activity and are thus useful in the treatment of conditions such as epilepsy. Compounds of this class are also useful for the treatment of glaucoma and peptic ulcers. Furthermore, pharmaceutical compositions containing a compound of formula (I) as well as methods for their use and novel intermediates are disclosed.

  通式 (I) 的化合物： 其中 R₁、R₂、R₃、R₄、R₅、R₆、n 和 p 如本文所定义；具有抗惊厥活性，因此可用于治疗癫痫等疾病。该类化合物还可用于治疗青光眼和消化性溃疡。此外，还公开了含有式（I）化合物的药物组合物及其使用方法和新型中间体。
• Imidate derivatives of pharmaceutically useful anticonvulsant sulfamates
  申请人：MCNEILAB, INC.

  公开号：EP0574256A1

  公开（公告）日：1993-12-15

  Imidate derivatives of sulfamates having the following formula (I): wherein R₁, R₂, R₃, R₄ and X are as herein defined have been found to be useful prodrug and exhibit anticonvulsant activity when converted to the active agent upon administration to a mammal and are thus useful in the treatment of conditions such as epilepsy. Further, the present invention encompasses pharmaceutical compositions containing a compound of formula (I) as well as methods for their use.

  具有下式 (I) 的氨基磺酸亚胺酯衍生物： 其中 R₁、R₂、R₃、R₄ 和 X 如本文所定义，已被发现是有用的原药，在给哺乳动物用药后转化为活性剂时表现出抗惊厥活性，因此可用于治疗癫痫等疾病。此外，本发明还包括含有式（I）化合物的药物组合物及其使用方法。
• Synthesis of hydroxylated derivatives of topiramate, a novel antiepileptic drug based on d-fructose: Investigation of oxidative metabolites
  作者：Samuel O. Nortey、Wu-Nan Wu、Bruce E. Maryanoff

  DOI：10.1016/s0008-6215(97)00214-0

  日期：1997.10

  To corroborate the structures of two monohydroxylated metabolites of topiramate (1), we synthesized four monosaccharide derivatives from D-fructose: 4,5-O-[(1R*)- and 4,5-O-[(1S* )-1-hydroxymethylethylidene]-2,3-O-isopropylidene-beta-D-fructopyranose sulfamates (2a and 2b); 2,3-O-[(1R*)- and 2,3-O-[(1R*)-1-hydroxymethylethylidene]-4,5-O-isopropylidene-beta-D-fructopyranose sulfamates (3a and 3b). The route to 2a and 2b was brief and straightforward, while that to 3a and 3b was more involved. In the latter case, the D-fructose bis-acetal 10 was benzylated and converted to a monoacetal dibenzoate (14) (50% yield), which was then transacetalized to give a mixture of 4,5-dibenzoyl-2,3-O-[(1R*)- and 4,5-dibenzoyl-2,3-O-[(1S* )-1-benzyloxymethylethylidene]-beta-D-fructopyranose (16a and 16b) (22%). The individual diastereomers were separated and processed via ester saponification, acetonation, sulfamoylation, and hydrogenolysis into 3a (36%) and 3b (27%). Structure 2b was confirmed for one oxidative metabolite, but the other metabolite was found not to correspond with either 2a, 3a, or 3b. On the basis of CI-MS and H-1 NMR data, a (2-hydroxy-1,4-dioxano)pyran structure, 4, is proposed for this unidentified metabolite. (C) 1997 Published by Elsevier Science Ltd.
• Non-chair six-membered-ring conformations. Preference for a twist-boat (or skew) structure in α-L-sorbopyranose derivatives
  作者：Michael J. Costanzo、Harold R. Almond、A.Diane Gauthier、Bruce E. Maryanoff

  DOI：10.1016/s0957-4166(00)80393-6

  日期：1994.12

  The conformational preferences for 2,3-O-isopropylidene-alpha-L-sorbopyranose derivatives 3-6 were determined by using H-1 NMR data and empirical force field calculations. Proton NMR studies of 3-6 indicate that a twist-boat (or skew) conformation (S-3(0)) prevails over possible chair forms for each compound. Force-field calculations (MM2, MNDO, AM1) on a model 2,3-O-isopropylidene-alpha-L-sorbopyranose system (18) indicate that the S-3(0) conform ation is among the low-energy structures. X-Ray crystallographic analysis of alpha-L-sorbopyranose sulfamate 3, a compound with potent anticonvulsant activity, demonstrates that the S-3(0) skew conformation is manifested in the solid state, as well.