1-金刚烷甲酸-D15 | 33830-12-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 1-金刚烷甲酸-D15
• 英文名称: adamantane-1-carboxylic-d15 acid
• 英文别名: Adamantan-d(15)-carboxylsaeure；1-adamantane-d15-carboxylic acid；pentadecadeuterio-adamantane-1-carboxylic acid；Adamantane-D15-carboxylic acid；2,2,3,4,4,5,6,6,7,8,8,9,9,10,10-pentadecadeuterioadamantane-1-carboxylic acid
• CAS: 33830-12-5
• 化学式: C₁₁H₁₆O₂
• 分子量: 195.128
• InChiKey: JIMXXGFJRDUSRO-BXSQCBKHSA-N

物化性质

• 熔点：
  170 - 173°C
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-金刚烷甲酸-D15 在 盐酸 、 lithium aluminium tetrahydride 、 盐酸羟胺 、 sodium acetate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 为溶剂， 反应 6.5h， 生成
  参考文献：
  名称：

  Specific Binding of Adamantane Drugs and Direction of Their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy

  摘要：

  The transmembrane domain of the influenza M2 protein (M2TM) forms a tetrameric proton channel important for the virus lifecycle. The proton-channel activity is inhibited by amine-containing adamantyl drugs amantadine and rimantadine, which have been shown to bind specifically to the pore of M2TM near Ser31. However, whether the polar amine points to the N- or C-terminus of the channel has not yet been determined. Elucidating the polar group direction will shed light on the mechanism by which drug binding inhibits this proton channel and will facilitate rational design of new inhibitors. In this study, we determine the polar amine direction using M2TM reconstituted in lipid bilayers as well as dodecylphosphocholine (D PC) micelles. C-13-H-2 rotational-echo double-resonance NMR experiments of C-13-labeled M2TM and methyl-deuterated rimantadine in lipid bilayers showed that the polar amine pointed to the C-terminus of the channel, with the methyl group close to Gly34. Solution NMR experiments of M2TM in DPC micelles indicate that drug binding causes significant chemical shift perturbations of the protein that are very similar to those seen for M2TM and M2(18-60) bound to lipid bilayers. Specific H-2-labeling of the drugs permitted the assignment of drug-protein cross peaks, which indicate that amantadine and rimantadine bind to the pore in the same fashion as for bilayer-bound M2TM. These results strongly suggest that adamantyl inhibition of M2TM is achieved not only by direct physical occlusion of the channel, but also by perturbing the equilibrium constant of the proton-sensing residue His37. The reproduction of the pharmacologically relevant specific pore-binding site in DPC micelles, which was not observed with a different detergent, DHPC, underscores the significant influence of the detergent environment on the functional structure of this membrane protein.

  DOI：

  10.1021/ja102581n
• 作为产物：
  描述：

  1-金刚烷甲酸 在 10% Pt/activated carbon 、 重水 、 水 、 sodium hydroxide 作用下， 以 异丙醇 为溶剂， 反应 48.0h， 以97%的产率得到1-金刚烷甲酸-D15
  参考文献：
  名称：

  轻度和直接多次氘标记饱和脂肪酸

  摘要：

  我们在异丙醇和氧化氘（i- PrOH）/ D的混合溶剂中建立了轻度直接的碳（Pt / C）铂催化的多氘标记的各种饱和脂肪酸，包括具有高氘效率的生物活性化合物在120°C的中性条件下为2 O，而无需外部添加氘或氢气。

  DOI：

  10.1002/adsc.201600363

文献信息

• 10.1021/acschemneuro.3c00850
  作者：Sparkes, Eric、Maloney, Callan J.、Markham, Jack W.、Dane, Chianna、Boyd, Rochelle、Gilchrist, Jayson、Moir, Michael、Gordon, Rebecca、Luo, Jia Lin、Pike, Edward、Walker, Katelyn A.、Kassiou, Michael、McGregor, Iain S.、Kevin, Richard C.、Hibbs, David E.、Jorgensen, William T.、Banister, Samuel D.、Cairns, Elizabeth A.、Ametovski, Adam

  DOI：10.1021/acschemneuro.3c00850

  日期：——

  Synthetic cannabinoid receptor agonists (SCRAs) are a growing class of new psychoactive substances (NPS) commonly derived from an N-alkylated indole, indazole, or 7-azaindole scaffold. Diversification of this core (at the 3-position) with amide-linked pendant amino acid groups and modular N-alkylation (of the indole/indazole/7-azaindole core) ensures that novel SCRAs continue to enter the illicit drug

  合成大麻素受体激动剂 (SCRA) 是一类不断增长的新型精神活性物质 (NPS)，通常源自N-烷基化吲哚、吲唑或 7-氮杂吲哚支架。该核心（在 3 位）具有酰胺连接的氨基酸侧基和模块化N-烷基化（吲哚/吲唑/7-氮杂吲哚核心）的多样化确保了新型 SCRA 继续快速进入非法药物市场。鉴于已检测到大量 SCRA，此类 NPS 的药理学评估已变得越来越普遍。自 2011 年以来，金刚烷衍生的 SCRA 一直出现在整个市场中，因此，系统地合成了这些衍生物并进行了药理学评估。制备氘代和氟化金刚烷衍生物以评估典型的氢生物等排体，以及评估新检测到的 AFUBIATA。
• Mild and Direct Multiple Deuterium-Labeling of Saturated Fatty Acids
  作者：Tsuyoshi Yamada、Kwihwan Park、Naoki Yasukawa、Kosuke Morita、Yasunari Monguchi、Yoshinari Sawama、Hironao Sajiki

  DOI：10.1002/adsc.201600363

  日期：2016.10.20

  established a mild and direct platinum on carbon (Pt/C)‐catalyzed multi‐deuterium labeling of various saturated fatty acids including bioactive compounds with high deuterium efficiencies in a mixed solvent of isopropyl alcohol and deuterium oxide (i‐PrOH)/D2O under neutral conditions at 120 °C without the external addition of deuterium or hydrogen gas.

  我们在异丙醇和氧化氘（i- PrOH）/ D的混合溶剂中建立了轻度直接的碳（Pt / C）铂催化的多氘标记的各种饱和脂肪酸，包括具有高氘效率的生物活性化合物在120°C的中性条件下为2 O，而无需外部添加氘或氢气。
• Specific Binding of Adamantane Drugs and Direction of Their Polar Amines in the Pore of the Influenza M2 Transmembrane Domain in Lipid Bilayers and Dodecylphosphocholine Micelles Determined by NMR Spectroscopy
  作者：Sarah D. Cady、Jun Wang、Yibing Wu、William F. DeGrado、Mei Hong

  DOI：10.1021/ja102581n

  日期：2011.3.30

  The transmembrane domain of the influenza M2 protein (M2TM) forms a tetrameric proton channel important for the virus lifecycle. The proton-channel activity is inhibited by amine-containing adamantyl drugs amantadine and rimantadine, which have been shown to bind specifically to the pore of M2TM near Ser31. However, whether the polar amine points to the N- or C-terminus of the channel has not yet been determined. Elucidating the polar group direction will shed light on the mechanism by which drug binding inhibits this proton channel and will facilitate rational design of new inhibitors. In this study, we determine the polar amine direction using M2TM reconstituted in lipid bilayers as well as dodecylphosphocholine (D PC) micelles. C-13-H-2 rotational-echo double-resonance NMR experiments of C-13-labeled M2TM and methyl-deuterated rimantadine in lipid bilayers showed that the polar amine pointed to the C-terminus of the channel, with the methyl group close to Gly34. Solution NMR experiments of M2TM in DPC micelles indicate that drug binding causes significant chemical shift perturbations of the protein that are very similar to those seen for M2TM and M2(18-60) bound to lipid bilayers. Specific H-2-labeling of the drugs permitted the assignment of drug-protein cross peaks, which indicate that amantadine and rimantadine bind to the pore in the same fashion as for bilayer-bound M2TM. These results strongly suggest that adamantyl inhibition of M2TM is achieved not only by direct physical occlusion of the channel, but also by perturbing the equilibrium constant of the proton-sensing residue His37. The reproduction of the pharmacologically relevant specific pore-binding site in DPC micelles, which was not observed with a different detergent, DHPC, underscores the significant influence of the detergent environment on the functional structure of this membrane protein.