Adamantanoyl-(1)-isocyanat | 69166-53-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: Adamantanoyl-(1)-isocyanat
• 英文别名: Adamantane-1-carbonyl isocyanate
• CAS: 69166-53-6
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: MQNQREVDODWBTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-氨基金刚烷 、 Adamantanoyl-(1)-isocyanat 以 甲苯 为溶剂， 生成 N-((adamantan-2-yl)carbamoyl)adamantane-1-carboxamide
  参考文献：
  名称：

  Novel acyl carbamates and acyl / diacyl ureas show in vitro efficacy against Toxoplasma gondii and Cryptosporidium parvum

  摘要：

  Toxoplasma gondii and Cryptosporidium parvum are protozoan parasites that are highly prevalent and opportunistically infect humans worldwide, but for which completely effective and safe medications are lacking. Herein, we synthesized a series of novel small molecules bearing the diacyl urea scaffold and related structures, and screened them for in vitro cytotoxicity and antiparasitic activity against T. gondii and C. parvum. We identified one compound (GMG-1-09), and four compounds (JS-1-09, JS-2-20, JS-2-35 and JS-2-49) with efficacy against C. parvum and T. gondii, respectively, at low micromolar concentrations and showed appreciable selectivity in human host cells. Among the four compounds with efficacy against T. gondii, JS-1-09 representing the diacyl urea scaffold was the most effective, with an anti-Toxoplasma IC₅₀ concentration (1.21 μM) that was nearly 53-fold lower than its cytotoxicity IC₅₀ concentration, indicating that this compound has a good selectivity index. The other three compounds (JS-2-20, JS-2-35 and JS-2-49) were structurally more divergent from JS-1-09 as they represent the acyl urea and acyl carbamate scaffold. This appeared to correlate with their anti-Toxoplasma activity, suggesting that these compounds' potency can likely be enhanced by selective structural modifications. One compound, GMG-1-09 representing acyl carbamate scaffold, depicted in vitro efficacy against C. parvum with an IC₅₀ concentration (32.24 μM) that was 14-fold lower than its cytotoxicity IC₅₀ concentration in a human intestinal cell line. Together, our studies unveil a series of novel synthetic acyl/diacyl urea and acyl carbamate scaffold-based small molecule compounds with micromolar activity against T. gondii and C. parvum that can be explored further for the development of the much-needed novel anti-protozoal drugs.

  DOI：

  10.1016/j.ijpddr.2020.08.006
• 作为产物：
  描述：

  1-金刚烷甲酸 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 Adamantanoyl-(1)-isocyanat
  参考文献：
  名称：

  精金化的有机硅杂环糖胺：表面修饰和抗原生动物活性的设计，合成和潜在评估†

  摘要：

  本研究评估设计和一系列organosilatranes的（的简便合成1-7与特权金刚烷基序，标记为“亲脂性子弹”拴），通过许多生物相容的键即酰胺，酯，硫酯，脲，硫脲，和硫代氨基甲酸酯基团。已通过元素分析，FT-IR和NMR（1 H和13 C）光谱以及质谱法对组装的硅烷基硅烷进行了严格的表征。单细胞原生动物，贾第鞭毛虫（G. lamblia）和阴道毛滴虫（T.阴道菌）引起的寄生虫病）代表主要的健康负担，因此对合成的化合物进行了体外杀菌和滴虫酸活性的检测。为此目的，首先使用吸收，分布，代谢，排泄和毒性（ADMET）工具仔细检查化合物的药代动力学概况，并且总体上讲，所有化合物均显示出良好的口服生物利用度。通过3-（4,5-二甲基噻唑基）-二苯基溴化四氮唑（MTT）分析，与标准药物（甲硝唑）相比，评估了新合成化合物的抗寄生虫活性。所有化合物均对IC 50表现出显着的抗兰伯氏菌和阴道锥虫的活性值分别在10

  DOI：

  10.1039/c7nj01456b

文献信息

• Synthesis of adamantane derivatives—VII
  作者：T. Sasaki、S. Eguchi、T. Toru

  DOI：10.1016/0040-4020(69)80033-5

  日期：1969.1

  adamantane-1-carbonyl isocyanate (XI) which was also produced by the reaction of Ia with an excess of oxalyl chloride in refluxing dichloromethane together with N,N′-bis(adamantane-1-carbonyl) oxalamide (XIII). The yields of XI and XIII depended on the molar ratio of oxalyl chloride to Ia. The reaction mechanism of carboxamides with oxalyl chloride as well as the mass spectra of adamantyl oxazolidine-4,5-dione

  用过量的草酰氯在二氯甲烷中处理金刚烷-1-甲酰胺（Ia，b），得到不稳定的恶唑啉-4,5-二酮衍生物（IIIa，b），将其转化为相应的恶唑烷-4,5-二酮衍生物（Va，b，VIII，IX和X），方法是用乙醇，苯酚，苯硫酚和炔丙醇处理。在回流的1,2-二氯乙烷中分解IIIa，得到金刚烷-1-羰基异氰酸酯（XI），这也是由Ia与过量的草酰氯在回流的二氯甲烷中与N，N'-双（金刚烷-1）反应生成的-羰基）草酰胺（XIII）。XI和XIII的产率取决于草酰氯与Ia的摩尔比。阐明了酰胺与草酰氯的反应机理以及金刚烷基恶唑烷-4,5-二酮衍生物的质谱。
• Adamantylated organosilatranes: design, synthesis, and potential appraisal in surface modification and anti-protozoal activity
  作者：Gurjaspreet Singh、Sunita Rani、Sanchita Gawri、Shweta Sinha、Rakesh Sehgal

  DOI：10.1039/c7nj01456b

  日期：——

  The present investigation evaluates the design and facile synthesis of a series of organosilatranes (1–7) tethered with the privileged adamantane motif, labelled as a ‘lipophilic bullet’, via numerous biocompatible linkages i.e. amide, ester, thioester, urea, thiourea, and thiocarbamate groups. The assembled silatranes have been scrupulously characterized by elemental analysis, FT-IR and NMR (1H and

  本研究评估设计和一系列organosilatranes的（的简便合成1-7与特权金刚烷基序，标记为“亲脂性子弹”拴），通过许多生物相容的键即酰胺，酯，硫酯，脲，硫脲，和硫代氨基甲酸酯基团。已通过元素分析，FT-IR和NMR（1 H和13 C）光谱以及质谱法对组装的硅烷基硅烷进行了严格的表征。单细胞原生动物，贾第鞭毛虫（G. lamblia）和阴道毛滴虫（T.阴道菌）引起的寄生虫病）代表主要的健康负担，因此对合成的化合物进行了体外杀菌和滴虫酸活性的检测。为此目的，首先使用吸收，分布，代谢，排泄和毒性（ADMET）工具仔细检查化合物的药代动力学概况，并且总体上讲，所有化合物均显示出良好的口服生物利用度。通过3-（4,5-二甲基噻唑基）-二苯基溴化四氮唑（MTT）分析，与标准药物（甲硝唑）相比，评估了新合成化合物的抗寄生虫活性。所有化合物均对IC 50表现出显着的抗兰伯氏菌和阴道锥虫的活性值分别在10
• Novel acyl carbamates and acyl / diacyl ureas show in vitro efficacy against Toxoplasma gondii and Cryptosporidium parvum
  作者：Kun Li、Gregory M. Grooms、Shahbaz M. Khan、Anolan Garcia Hernandez、William H. Witola、Jozef Stec

  DOI：10.1016/j.ijpddr.2020.08.006

  日期：2020.12

  Toxoplasma gondii and Cryptosporidium parvum are protozoan parasites that are highly prevalent and opportunistically infect humans worldwide, but for which completely effective and safe medications are lacking. Herein, we synthesized a series of novel small molecules bearing the diacyl urea scaffold and related structures, and screened them for in vitro cytotoxicity and antiparasitic activity against T. gondii and C. parvum. We identified one compound (GMG-1-09), and four compounds (JS-1-09, JS-2-20, JS-2-35 and JS-2-49) with efficacy against C. parvum and T. gondii, respectively, at low micromolar concentrations and showed appreciable selectivity in human host cells. Among the four compounds with efficacy against T. gondii, JS-1-09 representing the diacyl urea scaffold was the most effective, with an anti-Toxoplasma IC₅₀ concentration (1.21 μM) that was nearly 53-fold lower than its cytotoxicity IC₅₀ concentration, indicating that this compound has a good selectivity index. The other three compounds (JS-2-20, JS-2-35 and JS-2-49) were structurally more divergent from JS-1-09 as they represent the acyl urea and acyl carbamate scaffold. This appeared to correlate with their anti-Toxoplasma activity, suggesting that these compounds' potency can likely be enhanced by selective structural modifications. One compound, GMG-1-09 representing acyl carbamate scaffold, depicted in vitro efficacy against C. parvum with an IC₅₀ concentration (32.24 μM) that was 14-fold lower than its cytotoxicity IC₅₀ concentration in a human intestinal cell line. Together, our studies unveil a series of novel synthetic acyl/diacyl urea and acyl carbamate scaffold-based small molecule compounds with micromolar activity against T. gondii and C. parvum that can be explored further for the development of the much-needed novel anti-protozoal drugs.