carbamic acid, <1-(azidomethyl)-2-methylbutyl>-, 1,1-dimethylethyl ester, | 124590-30-3

• 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
• 英文名称: carbamic acid, <1-(azidomethyl)-2-methylbutyl>-, 1,1-dimethylethyl ester,
• 英文别名: carbamic acid, [1-(azidomethyl)-2-methylbutyl]-, 1,1-dimethylethyl ester, (S-(R*,R*))；tert-butyl N-[(2S,3S)-1-azido-3-methylpentan-2-yl]carbamate
• CAS: 124590-30-3
• 化学式: C₁₁H₂₂N₄O₂
• 分子量: 242.321
• InChiKey: MJYHIMZGJOLCFY-DTWKUNHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.24
• 重原子数：
  17.0
• 可旋转键数：
  5.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  87.09
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  carbamic acid, <1-(azidomethyl)-2-methylbutyl>-, 1,1-dimethylethyl ester, 在 Lindlar's catalyst 氢气 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以76%的产率得到carbamic acid, <1-(aminomethyl)-2-methylbutyl>-, 1,1-dimethylethyl ester,
  参考文献：
  名称：

  Evaluation of a vitamin-cloaking strategy for oligopeptide therapeutics: biotinylated HIV-1 protease inhibitors

  摘要：

  The outstanding limitations to the oligopeptide as a therapeutic agent are poor oral availability and rapid biliary clearance. To address these concerns a series of eight peptidic HIV-1 protease inhibitors containing the structural segment of the vitamin biotin have been prepared. These have been evaluated with regard to the hypothesis that this vitamin would cloak the peptidic character of these oligopeptides, and thus impart to these inhibitors the potential for absorption and distribution via biotin transporters and receptors. By iterative optimization about a -Chal psi[CH- (OH)CH(OH)]Val- core inhibitory insert, three particularly potent inhibitors (K-i less than or equal to 10 nM) of the HIV-1 protease were obtained. Although excellent cell culture antiviral activity is observed for other peptidic protease inhibitors of comparable affinity, none in this series exhibited satisfactory antiviral activity. This failure is-attributed to the incompatibility of the hydrophilic and hydrogen-bonding biotin segment, with the facile membrane permeability and intracellular access presumably required for antiviral activity. The ability of the biotin to cloak the peptide, and thus render the overall appearance of the conjugate as that of a vitamin, was evaluated. Four of this series were evaluated for recognition by the Caco-2 cell intestinal biotin transporter, None inhibited competitively biotin uptake, indicating a lack of recognition. A vitamin may bind to a specific protein carrier, and thus attain an improved serum profile (by resistance to biliary clearance) and advantageous delivery to cells. Therefore, the serum concentrations of three were evaluated following an iv bolus in a rat model for serum clearance. One of the three protease inhibitors (L-idonamide, 6-cyclohexyl-2,5,6-trideoxy-2-(1-methylethyl)-5-[[3-methyl-1-oxo-2-[[5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)-1-oxopentyl]amino]butyl]amino]-N-[2-methyl-1-[[(2-pyridinylmethyl)amino] carbonyl]butyl]-, [3aS-[3a alpha,4 beta(1R*,2R*;3R*),6a alpha]]-) sustained a more than 5-fold increase in serum concentration at all time points relative to the benchmark structure. The remaining two had serum concentrations at least equal to the benchmark, suggestive of improved resistance to clearance. One(L-idonamide, 6-cyclohexyl-2,5,6-trideoxy-5-[[2-[[5-(hexahydro-2-oxo-1H-thieno-[3,4-d]imidazol-4-yl)pentyl]thio]benzoyl]amino]-2-(1-methylethyl)-N-[2-methyl-1-[[(2-pyridinyl- methyl)amino]carbonyl]butyl]-, [3aS-[3a alpha,4 beta(1R*,2R*),6a alpha]]-) was prepared as a complex with the biotin-binding protein avidin. Avidin may resemble an endogenous serum biotin carrier protein. The antiviral activity (evaluated in an H9-HTLV(IIIB) acute HIV-1 infection assay) of the inhibitor and the avidin complex was identical. This suggests that the avidin-inhibitor complex is capable of cell internalization. Although the weak antiviral activity of these biotinylated inhibitors precludes consideration as practical HIV therapeutics, the overall data remain suggestive of vitamin cloaking of oligopeptides as a strategy of potential value.

  DOI：

  10.1021/jm00028a013
• 作为产物：
  描述：

  N-Boc-L-异亮氨醇 在 偶氮二甲酸二异丙酯 、 ZnN₆-pyridine2 、 三苯基膦 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以77%的产率得到carbamic acid, <1-(azidomethyl)-2-methylbutyl>-, 1,1-dimethylethyl ester,
  参考文献：
  名称：

  Evaluation of a vitamin-cloaking strategy for oligopeptide therapeutics: biotinylated HIV-1 protease inhibitors

  摘要：

  The outstanding limitations to the oligopeptide as a therapeutic agent are poor oral availability and rapid biliary clearance. To address these concerns a series of eight peptidic HIV-1 protease inhibitors containing the structural segment of the vitamin biotin have been prepared. These have been evaluated with regard to the hypothesis that this vitamin would cloak the peptidic character of these oligopeptides, and thus impart to these inhibitors the potential for absorption and distribution via biotin transporters and receptors. By iterative optimization about a -Chal psi[CH- (OH)CH(OH)]Val- core inhibitory insert, three particularly potent inhibitors (K-i less than or equal to 10 nM) of the HIV-1 protease were obtained. Although excellent cell culture antiviral activity is observed for other peptidic protease inhibitors of comparable affinity, none in this series exhibited satisfactory antiviral activity. This failure is-attributed to the incompatibility of the hydrophilic and hydrogen-bonding biotin segment, with the facile membrane permeability and intracellular access presumably required for antiviral activity. The ability of the biotin to cloak the peptide, and thus render the overall appearance of the conjugate as that of a vitamin, was evaluated. Four of this series were evaluated for recognition by the Caco-2 cell intestinal biotin transporter, None inhibited competitively biotin uptake, indicating a lack of recognition. A vitamin may bind to a specific protein carrier, and thus attain an improved serum profile (by resistance to biliary clearance) and advantageous delivery to cells. Therefore, the serum concentrations of three were evaluated following an iv bolus in a rat model for serum clearance. One of the three protease inhibitors (L-idonamide, 6-cyclohexyl-2,5,6-trideoxy-2-(1-methylethyl)-5-[[3-methyl-1-oxo-2-[[5-(hexahydro-2-oxo-1H-thieno[3,4-d]imidazol-4-yl)-1-oxopentyl]amino]butyl]amino]-N-[2-methyl-1-[[(2-pyridinylmethyl)amino] carbonyl]butyl]-, [3aS-[3a alpha,4 beta(1R*,2R*;3R*),6a alpha]]-) sustained a more than 5-fold increase in serum concentration at all time points relative to the benchmark structure. The remaining two had serum concentrations at least equal to the benchmark, suggestive of improved resistance to clearance. One(L-idonamide, 6-cyclohexyl-2,5,6-trideoxy-5-[[2-[[5-(hexahydro-2-oxo-1H-thieno-[3,4-d]imidazol-4-yl)pentyl]thio]benzoyl]amino]-2-(1-methylethyl)-N-[2-methyl-1-[[(2-pyridinyl- methyl)amino]carbonyl]butyl]-, [3aS-[3a alpha,4 beta(1R*,2R*),6a alpha]]-) was prepared as a complex with the biotin-binding protein avidin. Avidin may resemble an endogenous serum biotin carrier protein. The antiviral activity (evaluated in an H9-HTLV(IIIB) acute HIV-1 infection assay) of the inhibitor and the avidin complex was identical. This suggests that the avidin-inhibitor complex is capable of cell internalization. Although the weak antiviral activity of these biotinylated inhibitors precludes consideration as practical HIV therapeutics, the overall data remain suggestive of vitamin cloaking of oligopeptides as a strategy of potential value.

  DOI：

  10.1021/jm00028a013

文献信息

• Synthesis of New Chiral 4,5,6,7-Tetrahydro[1,2,3]triazolo[1,5-<i>a</i>]pyrazines from α-Amino Acid Derivatives under Mild Conditions
  作者：Debendra Mohapatra、Pradip Maity、Rajesh Gonnade、Mukund Chorghade、Mukund Gurjar

  DOI：10.1055/s-2007-984537

  日期：2007.7

  A practical and efficient regioselective synthesis of several new chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines is described from α -amino acid derivatives following intramolecular 'click' reaction as the key step. The method obviates product -purification; to obtain the pure triazole products, only the solvent needs to be evaporated.

  几种新的手性 4,5,6,7-四氢 [1,2,3] 三唑并 [1,5-a] 吡嗪的实用且有效的区域选择性合成描述为从分子内“点击”反应后的 α-氨基酸衍生物关键步骤。该方法避免了产品纯化；为获得纯三唑产品，只需蒸发溶剂即可。
• Synthesis of New Chiral 5,6,7,8-Tetrahydrotetrazolo[1,5-a]pyrazines from α-Amino Acid Derivatives Following “Click“ Chemistry
  作者：Debendra K. Mohapatra、Pradip K. Maity、Ravindra V. Ghorpade、Mukund K. Gurjar

  DOI：10.3987/com-08-s(f)121

  日期：——

  An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from alpha-amino acid derivatives.