sulfamic acid 1,7-heptanediyl ester | 96892-57-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫酸及其衍生物
• 英文名称: sulfamic acid 1,7-heptanediyl ester
• 英文别名: Hepsulfam；sulfamic acid 1,7-heptadiyl ester；1,7-Heptanediol bissulfamate；1,7-heptanediol disulfamate；7-sulfamoyloxyheptyl sulfamate
• CAS: 96892-57-8
• 化学式: C₇H₁₈N₂O₆S₂
• 分子量: 290.362
• InChiKey: GOJJWDOZNKBUSR-UHFFFAOYSA-N

物化性质

• 熔点：
  94-95 °C
• 沸点：
  478.2±55.0 °C(Predicted)
• 密度：
  1.407±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜
• 稳定性/保质期：
  Bulk: Test samples exposed to room temperature (25 °C) for three months shows very little degradation. Test samples stored at 50 °C in the dark showed significantly greater loss (g. 10 %). Solution: A test sample of 25 mg/mL in 30% DMSO /water showed no significant degradation when stored for 48 hr.

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  17
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  8

制备方法与用途

生物活性

Hepsulfam (NCI 329680; ZINC01574758) 是一种抗癌试剂，具有优异的抗白血病活性，在不同肿瘤中的中位 IC50 值为 0.91 μg/mL。

靶点

• IC50: 0.91 μg/mL (Tumors)

体外研究

在浓度为 1.0 μg/mL 的情况下，Hepsulfam 在克隆形成实验中对 37 种肿瘤中的 8 种（22%）表现出活性。Hepsulfam 对健康捐赠者的人类骨髓细胞（CFU-GM）显示出明确的体外毒性。进一步评估等毒浓度显示 Hepsulfam 特别在非小细胞肺癌中更具活性。Hepsulfam 对 L1210 白血病细胞的毒性大于其同源物 busulfan，一致的是，Hepsulfam 在 L1210 小鼠白血病细胞中诱导了 DNA 交叉链，而 busulfan 并未产生相同效果。此外，Hepsulfam 对两个人类白血病细胞系（111-60 和 K562）以及两个人类结肠癌细胞系（BE 和 HT-29）的毒性也大于 busulfan。与 L1210 细胞的情况类似，在降低 10 倍浓度并增加药物暴露时间至 12 小时后，Hepsulfam 对人类白血病细胞系的毒性更高。

体内研究

在大细胞肺癌异种移植和胃癌模型中，Hepsulfam 表现出优于 busulfan 的体内活性。预临床研究表明 Hepsulfam 可能对该治疗固体人体恶性肿瘤起到一定作用。然而，与 busulfan 相比，Hepsulfam 增加的骨髓毒性可能对其进一步临床应用具有重要意义。

反应信息

• 作为反应物：
  描述：

  sulfamic acid 1,7-heptanediyl ester 在 水 作用下， 生成 sulfamic acid 1,7-heptamonoyl ester
  参考文献：
  名称：

  水和富含18氧的水中氨基磺酸1,7-庚二酯（一种实验性细胞毒剂）的降解机理研究

  摘要：

  氨基磺酸1,7-庚二酯的水解降解是在47°C的水中和富含18O的水中进行的。在恒定的离子强度下，在2.5至8.0的各种pH值下，也研究了1的降解。 0.15 M）和温度（25摄氏度）。水解是一级反应，与pH无关，观察到的平均（+/- SD）速率常数（kobs）为2.38 +/- 0.6 X 10（-3）h-1。没有观察到明显的缓冲液催化作用。根据TLC，HPLC和质谱研究，1最初降解为氨基磺酸1,7-庚烷单基酯，随后降解为1,7-庚二醇。通过富集18 O的水反应混合物的质谱法评估键裂解的位点。观察到独家的C-O键裂变。可以假定几种降解1的机理。

  DOI：

  10.1002/jps.2600760216
• 作为产物：
  描述：

  1,7-庚二醇 在 氨基磺酰氯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 生成 sulfamic acid 1,7-heptanediyl ester
  参考文献：
  名称：

  Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/tumor-associated carbonic anhydrase isozymes I, II, and IX with bis-sulfamates

  摘要：

  A series of bis-sulfamates incorporating aliphatic, aromatic, or betulinyl moieties in their molecules was obtained by reaction of the corresponding diols/diphenols with sulfamoyl chloride. The library of bis-sulfamates thus obtained was tested for the inhibition of three physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, the cytosolic hCA I and II, and the transmembrane, tumor-associated hCA IX. The new compounds reported here inhibited hCA I with K-I s in the range of 79 nM-16.45 muM, hCA II with K-I s in the range of 6-643 nM, and hCA IX with K-I s in the range of 4-5400 nM. Several low nanomolar hCA IX inhibitors were detected, such as 1,8-octylene-bis-sulfamate or 1,10-decylene-bis-sulfamate (K-I s in the range of 4-7 nM), which showed good selectivity ratios (in the range of 3.50-3.85) for hCA IX over hCA II inhibition. The most selective hCA IX inhibitor was phenyl-1,4-dimethylene-bis-sulfamate (K-I of 61.6 nM), which was a 10.43 times better hCA IX than hCA II inhibitor. These derivatives are interesting candidates for the development of novel antitumor therapies targeting hypoxic tumors, since hCA IX is highly overexpressed in such tissues, and its presence is correlated with bad prognosis and unfavorable clinical outcome. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.11.058

文献信息

• Sulfamates as antiglaucoma agents
  申请人：A. H. Robins Company, Incorporated

  公开号：US05192785A1

  公开（公告）日：1993-03-09

  Sulfamate esters of the formula (HO).sub.p --A--[OSO.sub.2 NR.sup.1 R.sup.2 ].sub.z where A is aryloxyalkyl, p is the number of unreacted hydroxy groups present on the alkyl moiety and may be zero, z is the number of --OS(O).sub.2 NR.sup.1 R.sup.2 groups attached to carbons of the alkyl moiety and is always at least one; R.sup.1 and R.sup.2 are selected from hydrogen, loweralkyl, carboxy, and the like are useful in treating glaucoma.

  公式为(HO).sub.p --A--[OSO.sub.2 NR.sup.1 R.sup.2 ].sub.z的磺酰胺酯，其中A为芳氧基烷基，p是烷基部分未反应的羟基数，可以为零，z为连接到烷基部分碳上的--OS(O).sub.2 NR.sup.1 R.sup.2基团数，且始终至少为1；R.sup.1和R.sup.2从氢、低碳基、羧基等中选择，可用于治疗青光眼。
• Compounds having one or more aminosulfonyloxy radicals useful as
  申请人：A. H. Robins Company, Incorporated

  公开号：US05273993A1

  公开（公告）日：1993-12-28

  Methods of treating chronic arthritis and osteoporosis which utilize both known and novel compounds which would fall under the general formula: (HO)p--A--[--OS(O).sub.2 NR.sup.1 R.sup.2 ].sub.z wherein A encompasses a wide range of values including but not limited to aryl, loweralkyl, cycloalkyl, and carbohydrates including sucrose and fructose; p is equal to the number of unreacted hydroxy groups contained on the molecule and may be zero; z is the number of --OS(O).sub.2 NR.sup.1 R.sup.2 groups and is always at least one; R.sup.1 and R.sup.2 are selected from hydrogen, loweralkyl, carboxy and the like; a novel process for preparing the compounds is provided wherein an appropriate sulfamic acid aryl ester is reacted with a hydroxy substituted A radical which may or may not contain thereon protected carboxyl, amino or hydroxy substituents, in an aprotic solvent containing a tertiary amine base. Pharmaceutical compositions for the treatment of chronic arthritis and osteoporosis are also provided.

  本发明涉及治疗慢性关节炎和骨质疏松症的方法，利用已知和新颖化合物，这些化合物可归为以下一般式：（HO）p-A-[-OS（O）.sub.2 NR.sup.1 R.sup.2].sub.z，其中A包括一系列值，包括但不限于芳基，低烷基，环烷基和碳水化合物，包括蔗糖和果糖；p等于分子中未反应的羟基数，可以为零；z是-OS（O）.sub.2 NR.sup.1 R.sup.2基团的数量，始终至少为一；R.sup.1和R.sup.2从氢，低烷基，羧基等中选择；提供了一种新颖的制备该化合物的过程，其中适当的磺酸芳基酯与含有保护羧基，氨基或羟基取代基团的羟基取代A基团在无极溶剂中反应，其中含有三级胺碱。还提供了用于治疗慢性关节炎和骨质疏松症的药物组合物。
• Method for treating malignant conditions
  申请人：Sterling Drug Inc.

  公开号：US04829084A1

  公开（公告）日：1989-05-09

  A method for inhibiting the growth of malignant cells in a mammal, said cells being susceptible to the action of a compound of the formula H.sub.2 NSO.sub.2 O(CH.sub.2).sub.n OSO.sub.2 NH.sub.2 where n is 6-8, which comprises administering to said mammal an antineoplastically effective amount of said compound incorporated in a suitable pharmaceutically acceptable excipient. The compounds are particularly effective against malignant cells derived from or associated with leukemia, mammary tumors, melanoma or colon adenocarcinoma.

  一种抑制哺乳动物恶性细胞生长的方法，所述细胞易受到化合物H.sub.2 NSO.sub.2 O(CH.sub.2).sub.n OSO.sub.2 NH.sub.2的作用，其中n为6-8，所述方法包括向所述哺乳动物施用所述化合物在适宜的药用载体中所含的抗肿瘤有效量。该化合物对于源自或与白血病、乳腺肿瘤、黑色素瘤或结肠腺癌相关的恶性细胞特别有效。
• Disulfamate for treating malignant conditions
  申请人：STERLING DRUG INC.

  公开号：EP0147540A2

  公开（公告）日：1985-07-10

  A compound for inhibiting the growth of malignant cells in a mammal comprising an alkanediol disulfamate of the formula where n = 6-8, inclusive.

  一种用于抑制哺乳动物体内恶性细胞生长的化合物，包含一种烷二醇二氨基磺酸酯，其式中 n = 6-8 （包括 6-8）。
• Use of treosulfan and derivaties thereof for treating multiple sclerosis
  申请人：Sass Gretel

  公开号：US20060041015A1

  公开（公告）日：2006-02-23

  The invention relates to the use of treosulfan and/or derivatives thereof for producing a pharmaceutical composition used in the treatment of multiple sclerosis.

  本发明涉及使用硫丹和/或其衍生物生产用于治疗多发性硬化症的药物组合物。