2-((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazinecarbothioamide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazinecarbothioamide
• 英文别名: 2-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazinecarbothioamide；(+)-camphor thiosemicarbazone；(1R)-bornan-2-one thiosemicarbazone；(1R)-Bornan-2-on-thiosemicarbazon；[[(1R,4R)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanylidene]amino]thiourea
• 化学式: C₁₁H₁₉N₃S
• 分子量: 225.358
• InChiKey: HFTWOMIQZXSECJ-HQJQHLMTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazinecarbothioamide 在 氯化亚砜 作用下， 以60%的产率得到
  参考文献：
  名称：

  A New Type of Synthesis of 1,2,3-Thiadiazole and 1,2,3-Diazaphosphole Derivatives Via-Hurd-Mori Cyclization

  摘要：

  我们提出了一种简短高效的合成方法，从廉价且易得的樟脑和苯乙酮衍生物开始合成标题化合物。优化的步骤允许在几个步骤内大规模制备这种新型合成物。通过相应的半羧肼6-10，从酮1-5制备了新的1,2,3-噻二唑和1,2,3-二氮磷杂环衍生物11-20。分别使用了Hurd-Mori和Lalezari方法来制备这些1,2,3-噻二唑和1,2,3-二氮磷杂环衍生物。这些衍生物由于具有高潜在的生物活性，展现出抗癌效果。

  DOI：

  10.1155/2012/457949
• 作为产物：
  描述：

  白樟油 、 氨基硫脲 以 乙醇 为溶剂， 反应 1.0h， 生成 2-((1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazinecarbothioamide
  参考文献：
  名称：

  松萝酸与单萜类化合物作为强效酪氨酰 DNA 磷酸二酯酶 1 抑制剂。

  摘要：

  由天然和合成等价物的不同药效团产生的混合分子已成功用于制药实践。抗癌治疗的一个有希望的靶点是酪氨酰 DNA 磷酸二酯酶 1 (Tdp1)，因为它可以修复由 DNA 拓扑异构酶 1 (Top1) 抑制剂引起的 DNA 损伤，从而导致耐药性。在这项研究中，通过结合一组具有 Tdp1 抑制特性的天然化合物的药效部分，特别是酚松香酸和一组不同的单萜类片段，合成了新的杂化化合物。这些片段通过肼基噻唑接头连接。新化合物的抑制特性主要取决于萜类化合物的结构。两种最有效的化合物，9a和9b, 由柠檬醛和香茅醛合成，其中包含 IC 50值在 10-16 nM 范围内的无环片段。一些合成的衍生物对 HeLa 细胞显示出低细胞毒性，并将 Top1 抑制剂拓扑替康的体外作用提高了三到七倍。当与 Top1 抑制剂联合使用时，这些衍生物可能被认为是开发抗癌疗法的潜在药物。

  DOI：

  10.1021/acs.jnatprod.9b01089

文献信息

• Synthesis and antiviral activity of camphor-based 1,3-thiazolidin-4-one and thiazole derivatives as <i>Orthopoxvirus</i>-reproduction inhibitors
  作者：Anastasiya S. Sokolova、Olga I. Yarovaya、Nikolay I. Bormotov、Larisa N. Shishkina、Nariman F. Salakhutdinov

  DOI：10.1039/c8md00347e

  日期：——

  nitrogen–sulphur containing heterocycles such as 1,3-thiazolidin-4-one and thiazoles containing a 1,7,7-trimethylbicyclo[2.2.1]heptan scaffold were synthesized and screened for their antiviral activity. The bioassay results showed that the 4b, 4c and 4e thiazoles, which contained a substituted benzene ring, were able to inhibit VV reproduction with IC50 values in the 2.4–3.7 micromolar range whilst exhibiting

  正痘病毒属属于痘病毒科，包括天花病毒（天花）、牛痘病毒、猴痘病毒和牛痘病毒（VV）。天花被认为是人类历史上最大的流行病祸害之一。目前已被根除；然而，作为生物战或生物恐怖武器，它仍然是一个相当大的威胁。痘病毒 VV 作为模型病毒，可​​以从中鉴定出针对正痘病毒的新抗病毒疗法。在此，合成了一系列含氮硫杂环化合物，例如 1,3-thiazolidin-4-one 和含有 1,7,7-三甲基双环[2.2.1]庚烷支架的噻唑，并筛选了其抗病毒活性。生物测定结果表明，含有取代苯环的4b 、 4c和4e噻唑能够抑制VV繁殖，IC 50值在2.4-3.7微摩尔范围内，同时表现出中等的细胞毒性。在噻唑烷-4-酮衍生物中，含有4-甲基亚苄基的化合物8b表现出良好的抑制活性（IC 50 = 9.5 μM）和中等毒性。
• Synthesis, In Vitro Biological Screening and Molecular Docking Studies of Novel Camphor-Based Thiazoles
  作者：Krzysztof Laczkowski、Konrad Misiura、Anna Biernasiuk、Anna Malm、Agata Siwek、Tomasz Plech、Emilia Ciok-Pater、Krzysztof Skowron、Eugenia Gospodarek

  DOI：10.2174/15734064113096660054

  日期：2014.8.4

  Synthesis, characterization and investigation of antibacterial and antifungal activities of twelve camphor based 2,4-disubstituted 1,3-thiazoles is presented. Their structures were determined using NMR, IR, FAB MS and HRMS analyses. Among the derivatives, 3i and 5 were found to exhibit antifungal and antibacterial activities comparable to that of fluconazole and ciprofloxacin against yeast belonging to Candida spp., MIC 0.12-0.98 μg/ml and Gram-positive bacteria including both pathogenic S. aureus and opportunistic S. epidermidis, MIC 0.98-7.81 μg/ml, B. subtilis and B. cereus, MIC 3.91-31.25 μg/ml, and M. luteus, MIC 0.98 μg/ml species, respectively. Molecular docking studies of all compounds into the active sites of microbial enzymes indicated a possible targets SAP and NMT, thiazoles 3a-j, 4, 5 showed more favourable affinity than the native ligand.

  本文介绍了十二种樟脑基2,4-二取代1,3-噻唑的合成、表征及其抗菌和抗真菌活性研究。它们的结构通过NMR、IR、FAB MS和HRMS分析确定。在这些衍生物中，3i和5表现出与氟康唑和环丙沙星相当的抗真菌和抗菌活性，对属于念珠菌属的酵母菌（MIC 0.12-0.98 μg/ml）、包括致病性金黄色葡萄球菌和机会性表皮葡萄球菌在内的革兰氏阳性细菌（MIC 0.98-7.81 μg/ml）、枯草芽孢杆菌和蜡样芽孢杆菌（MIC 3.91-31.25 μg/ml）以及藤黄微球菌（MIC 0.98 μg/ml）具有活性。所有化合物的分子对接研究显示，它们与微生物酶的活性位点结合，可能的目标是SAP和NMT，噻唑3a-j、4、5显示出比原生配体更有利的亲和性。
• Environmental controls of NDVI and sheep production in the Tierra del Fuego steppe of Argentina
  作者：Gabriela Posse、Ana María Cingolani

  DOI：10.2307/1479004

  日期：2000.12

  Abstract. We analysed vegetation dynamics in Tierra del Fuego steppes using Normalized Difference Vegetation Index (NDVI) data provided by advanced very high‐resolution radiometer (AVHRR) on board the National Oceanic and Atmospheric Administration (NOAA) polar satellite. Our objective, at a regional scale, was to analyse the spatial variability of NDVI dynamics in relation to parent material and geographic location, representing the fertility and climate gradients respectively; at a local scale, it was to analyse the inter‐annual variability associated with climate and its relation with sheep production indices. The general pattern of NDVI dynamics was analysed with Principal Component Analysis. We found that the geographic location was more important than landscape type in explaining NDVI dynamics despite the fact that the variation in landscape type reflects a fertility gradient strongly associated with floristic composition and secondary productivity.Discriminant Analysis was performed to identify the variables that better distinguish geographic units. The Northern region (with the lowest precipitation and the highest temperatures) had lower NDVI values over the year. In the Central region, NDVI reached the highest value of the season, surpassing both other regions. The Southern region (the coldest and moistest) had its growth pattern displaced towards the summer. For the Central region we analysed 10 years of monthly NDVI data with PCA. We found that precipitation from August to December and winter temperature are the most important determinants of overall NDVI values. Lamb production was correlated with spring and early summer NDVI values. Sheep mortality is affected by low NDVI values in late summer and high annual amplitude. Satellite information allowed us to characterize the vegetation dynamics of three ecological areas across the Fuegian steppe.
• A New Type of Synthesis of 1,2,3-Thiadiazole and 1,2,3-Diazaphosphole Derivatives Via-Hurd-Mori Cyclization
  作者：Mona A. Hosny、Taghreed H. El-Sayed、Emtithal El-Sawi

  DOI：10.1155/2012/457949

  日期：——

  We present a short and efficient synthesis of the title compounds starting with cheap and readily available camphor and derivatives of acetophenone. The optimized sequence allows the large-scale preparation of this new type of synthesis in a few steps. New 1,2,3-thiadiazole and 1,2,3-diazaphosphole derivatives 11-20, were prepared from the ketones 1-5 via the corresponding semicarbazones 6-10. The Hurd-Mori and Lalezari methods were used, respectively, for the preparation of these 1,2,3-thiadiazole and 1,2,3-diazaphospholene derivatives. These derivatives exhibit anticancer effect due to their high potential biological activity.

  我们提出了一种简短高效的合成方法，从廉价且易得的樟脑和苯乙酮衍生物开始合成标题化合物。优化的步骤允许在几个步骤内大规模制备这种新型合成物。通过相应的半羧肼6-10，从酮1-5制备了新的1,2,3-噻二唑和1,2,3-二氮磷杂环衍生物11-20。分别使用了Hurd-Mori和Lalezari方法来制备这些1,2,3-噻二唑和1,2,3-二氮磷杂环衍生物。这些衍生物由于具有高潜在的生物活性，展现出抗癌效果。
• Usnic Acid Conjugates with Monoterpenoids as Potent Tyrosyl-DNA Phosphodiesterase 1 Inhibitors
  作者：Olga Luzina、Alexander Filimonov、Alexandra Zakharenko、Arina Chepanova、Olga Zakharova、Ekaterina Ilina、Nadezhda Dyrkheeva、Galina Likhatskaya、Nariman Salakhutdinov、Olga Lavrik

  DOI：10.1021/acs.jnatprod.9b01089

  日期：2020.8.28

  monoterpenoid fragments. These fragments were connected through a hydrazinothiazole linker. The inhibitory properties of the new compounds mainly depended on the structure of the terpenoid moieties. The two most potent compounds, 9a and 9b, were synthesized from citral and citronellal, which contain acyclic fragments with IC50 values in the range of 10–16 nM. Some synthesized derivatives showed low cytotoxicity

  由天然和合成等价物的不同药效团产生的混合分子已成功用于制药实践。抗癌治疗的一个有希望的靶点是酪氨酰 DNA 磷酸二酯酶 1 (Tdp1)，因为它可以修复由 DNA 拓扑异构酶 1 (Top1) 抑制剂引起的 DNA 损伤，从而导致耐药性。在这项研究中，通过结合一组具有 Tdp1 抑制特性的天然化合物的药效部分，特别是酚松香酸和一组不同的单萜类片段，合成了新的杂化化合物。这些片段通过肼基噻唑接头连接。新化合物的抑制特性主要取决于萜类化合物的结构。两种最有效的化合物，9a和9b, 由柠檬醛和香茅醛合成，其中包含 IC 50值在 10-16 nM 范围内的无环片段。一些合成的衍生物对 HeLa 细胞显示出低细胞毒性，并将 Top1 抑制剂拓扑替康的体外作用提高了三到七倍。当与 Top1 抑制剂联合使用时，这些衍生物可能被认为是开发抗癌疗法的潜在药物。