2-adamantane-1-carbonyl N-phenylhydrazine carbothioamide | 139158-44-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-adamantane-1-carbonyl N-phenylhydrazine carbothioamide
• 英文别名: 2-(1-Adamantylcarbonyl)-N-phenylhydrazinecarbothioamide；1-(adamantane-1-carbonylamino)-3-phenylthiourea
• CAS: 139158-44-4
• 化学式: C₁₈H₂₃N₃OS
• 分子量: 329.466
• InChiKey: FHEDTWXEHBPTNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  85.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-adamantane-1-carbonyl N-phenylhydrazine carbothioamide 在 sodium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 生成 5-Adamantan-1-yl-4-phenyl-4H-[1,2,4]triazole-3-thiol
  参考文献：
  名称：

  作为潜在 11β-HSD1 抑制剂的金刚烷连接 1,2,4-三唑衍生物的结构见解和对接分析

  摘要：

  介绍了三种金刚烷连接的1,2,4-三唑衍生物的固态结构分析和对接研究。晶体结构分析表明，化合物2结晶在三斜晶系P -1 空间群，而化合物1和3则结晶在相同的单斜晶系P 2 1 / c空间群。由于它们之间的唯一区别是芳基上的对位取代，这些NO 2和卤素基团的电子性质似乎对固体的形成没有影响。然而，由于NO 2 /Cl取代的分子之间相似的分子间配置，与基团大小的可能相关性并未被丢弃。尽管有相似之处，CE-B3LYP 能量模型计算表明，它们之间的成对相互作用能量有所不同，因此总堆积能量受到影响。 HOMO-LUMO 计算的能量表明，NO 2基团影响反应特性，使分子具有柔软性并具有接受电子的最佳配置。此外，计算机模拟研究预测这些化合物可能能够抑制 11β-HSD1 酶，该酶与肥胖和糖尿病有关。自我对接和交叉对接实验表明，许多非天然 11β-HSD1 抑制剂能够准确对接在 11β-HSD1 X 射线结构4C7J内。与4C7J天然配体

  DOI：

  10.3390/molecules26175335
• 作为产物：
  描述：

  金刚烷-1-甲酰肼 、 硫代异氰酸苯酯 以 乙醇 为溶剂， 生成 2-adamantane-1-carbonyl N-phenylhydrazine carbothioamide
  参考文献：
  名称：

  作为潜在 11β-HSD1 抑制剂的金刚烷连接 1,2,4-三唑衍生物的结构见解和对接分析

  摘要：

  介绍了三种金刚烷连接的1,2,4-三唑衍生物的固态结构分析和对接研究。晶体结构分析表明，化合物2结晶在三斜晶系P -1 空间群，而化合物1和3则结晶在相同的单斜晶系P 2 1 / c空间群。由于它们之间的唯一区别是芳基上的对位取代，这些NO 2和卤素基团的电子性质似乎对固体的形成没有影响。然而，由于NO 2 /Cl取代的分子之间相似的分子间配置，与基团大小的可能相关性并未被丢弃。尽管有相似之处，CE-B3LYP 能量模型计算表明，它们之间的成对相互作用能量有所不同，因此总堆积能量受到影响。 HOMO-LUMO 计算的能量表明，NO 2基团影响反应特性，使分子具有柔软性并具有接受电子的最佳配置。此外，计算机模拟研究预测这些化合物可能能够抑制 11β-HSD1 酶，该酶与肥胖和糖尿病有关。自我对接和交叉对接实验表明，许多非天然 11β-HSD1 抑制剂能够准确对接在 11β-HSD1 X 射线结构4C7J内。与4C7J天然配体

  DOI：

  10.3390/molecules26175335

文献信息

• 11-Beta-hydroxysteroid dehydrogenase 1 inhibitors useful for the treatment of diabetes, obesity and dyslipidemia
  申请人：Balkovec M. James

  公开号：US20050070720A1

  公开（公告）日：2005-03-31

  Compounds having Formula (I), including pharmaceutically acceptable salts and prodrugs thereof: are selective inhibitors of the 11β-HSD1 enzyme. They inhibit the 11β-HSD1-mediated conversion of cortisone and other 11-keto-glucocorticoids to cortisol and other 11β-hydroxy-glucocorticoids. The 11β-HSD1 inhibitors therefore decrease the amount of cortisol in target tissues, thereby modulating the effects of cortisol. Modulation of cortisol may be effective in controlling non-insulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Syndrome X, and other symptoms associated with NIDDM or with excess cortisol in the body.

  化合物公式为（I）的化合物，包括其药学上可接受的盐和前药：是11β-HSD1酶的选择性抑制剂。它们抑制11β-HSD1介导的可的松和其他11-酮基-糖皮质激素转化为皮质醇和其他11β-羟基-糖皮质激素的过程。因此，11β-HSD1抑制剂减少了目标组织中皮质醇的含量，从而调节了皮质醇的效应。调节皮质醇可能对控制非胰岛素依赖性糖尿病（NIDDM）、高血糖、肥胖症、胰岛素抵抗、血脂异常、高脂血症、高血压、X综合征和与体内过多皮质醇有关的其他症状有效。
• 11-β-hydroxysteroid dehydrogenase 1 inhibitors useful for the treatment of diabetes, obesity and dyslipidemia
  申请人：Merck & Co., Inc.

  公开号：US07329683B2

  公开（公告）日：2008-02-12

  Compounds having Formula (I), including pharmaceutically acceptable salts and prodrugs thereof: are selective inhibitors of the 11β-HSD1 enzyme. They inhibit the 11β-HSD1-mediated conversion of cortisone and other 11-keto-glucocorticoids to cortisol and other 11β-hydroxy-glucocorticoids. The 11β-HSD1 inhibitors therefore decrease the amount of cortisol in target tissues, thereby modulating the effects of cortisol. Modulation of cortisol may be effective in controlling non-insulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dyslipidemia, hyperlipidemia, hypertension, Syndrome X, and other symptoms associated with NIDDM or with excess cortisol in the body

  化合物公式(I)的化合物，包括其药学上可接受的盐和前药：是11β-HSD1酶的选择性抑制剂。它们抑制11β-HSD1介导的可的松和其他11-酮基-糖皮质激素转化为皮质醇和其他11β-羟基-糖皮质激素的过程。因此，11β-HSD1抑制剂减少了目标组织中皮质醇的量，从而调节了皮质醇的作用。调节皮质醇可能对控制非胰岛素依赖性糖尿病（NIDDM）、高血糖、肥胖症、胰岛素抵抗、血脂异常、高脂血症、高血压、X综合症和与体内过量皮质醇相关的其他症状有效。
• El-Emam; Ibrahim, Arzneimittel-Forschung/Drug Research, 1991, vol. 41, # 12, p. 1260 - 1264
  作者：El-Emam、Ibrahim

  DOI：——

  日期：——
• A novel adamantane thiadiazole derivative induces mitochondria-mediated apoptosis in lung carcinoma cell line
  作者：Ayat G. Ali、Magda F. Mohamed、Abdou O. Abdelhamid、Mervat S. Mohamed

  DOI：10.1016/j.bmc.2016.10.040

  日期：2017.1

  The interaction of organic compounds with apoptosis regulatory proteins is an attractive field of research because of its relevance in the development of new chemotherapeutic agents for cancer treatment. Our group designed four new adamantane thiadiazole derivatives (ATDs). The four ATDs were theoretically tested for their binding affinities to a model of an apoptosis inhibitor protein using molecular modeling. ATD-4 which interacted with the highest binding affinity was synthesized and characterized. The in vitro cytotoxicity of ATD-4 against different cancer cell lines as well as normal cell line was determined and compared with 5-fluorouracil as a standard positive control. The lung carcinoma cell line that showed the highest cytotoxic activity due to ATD-4 treatment was chosen to further study if ATD-4 can perform its cytotoxic activity through the induction of apoptosis as expected from molecular modeling. Inducing apoptosis by ATD-4 in lung carcinoma cell line was assessed by various biochemical and morphological characteristics. Biochemically: The effect of ATD-4 on cell cycle and its ability to induce apoptosis were checked through flow cytometry. Caspase-3 activity was detected by a colorimetric method. Real timepolymerase chain reaction (q-PCR) was used to detect p53, caspase-3, bcl-2 and bax gene expression. Morphologically: Changes in cell surface morphology, granulation and average surface roughness were detected using atomic force microscopy (AFM). Cell shrinkage, increase in cytoplasmic organelles, changes in mitochondrial number and morphology, chromatin condensation, membrane blebbing and formation of apoptotic bodies were detected using transmission electron microscopy (TEM). The obtained results suggest that ATD-4 exerted its antitumor activity against A549 cells through the induction of the intrinsic (mitochondrial) apoptotic pathway. (C) 2016 Elsevier Ltd. All rights reserved.
• EP1474139A4
  申请人：——

  公开号：EP1474139A4

  公开（公告）日：2005-06-29