(+)-Azietomidate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (+)-Azietomidate
• 英文别名: 2-(3-methyldiazirin-3-yl)ethyl 3-[(1R)-1-phenylethyl]imidazole-4-carboxylate
• 化学式: C₁₆H₁₈N₄O₂
• 分子量: 298.345
• InChiKey: DUOHNSBKYJHAMQ-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  依托咪酯	etomidate	33125-97-2	C14H16N2O2	244.293
  1-[(1R)-1-苯基乙基]-1H-咪唑-5-羧酸	(R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid	56649-48-0	C12H12N2O2	216.239

反应信息

• 作为产物：
  描述：

  依托咪酯 在 4-二甲氨基吡啶 、 sodium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 (+)-Azietomidate
  参考文献：
  名称：

  2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate:  A Derivative of the Stereoselective General Anesthetic Etomidate for Photolabeling Ligand-Gated Ion Channels

  摘要：

  To locate general anesthetic binding sites on ligand-gated ion channels, a diazirine derivative of the potent intravenous anesthetic, R-(+)-etomidate (2-ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate), has been synthesized and characterized. R-(+)-Azietomidate [2-(3-methyl-3H-diaziren-3-yl)ethyl 1-(l-phenylethyl)-1H-imidazole-5-carboxylate] anesthetizes tadpoles with an EC50 of 2.2 muM, identical to that of R-(+)-etomidate. At this concentration both agents equally enhanced GABA-induced currents and decreased binding of the caged-convulsant [S-35]TBPS to GABA(A) receptors. In all of the above actions R-(+)-azietomidate is about an order of magnitude more potent than S-(-)-azietomidate, an enantioselectivity comparable to etomidate's. R-(+)-Azietomidate also inhibits acetylcholine-induced currents in nicotinic acetylcholine receptors, with about twice the potency of the parent compound. [H-3]Azietomidate photoincorporated into Torpedo nicotinic acetylcholine receptor-rich membranes. Desensitization decreased photoincorporation into the delta-subunit and increased that into the alpha-subunit. The latter increase was confined to a proteolytic fragment containing the first three transmembrane segments. Thus, R-(+)-azietomidate is a potent stereoselective general anesthetic and an effective photolabel.

  DOI：

  10.1021/jm020465v

文献信息

• 2-(3-Methyl-3<i>H</i>-diaziren-3-yl)ethyl 1-(1-phenylethyl)-1<i>H</i>-imidazole-5-carboxylate:  A Derivative of the Stereoselective General Anesthetic Etomidate for Photolabeling Ligand-Gated Ion Channels
  作者：S. Shaukat Husain、Michael R. Ziebell、Dirk Ruesch、Filbert Hong、Enrique Arevalo、Jonathan A. Kosterlitz、Richard W. Olsen、Stuart A. Forman、Jonathan B. Cohen、Keith W. Miller

  DOI：10.1021/jm020465v

  日期：2003.3.1

  To locate general anesthetic binding sites on ligand-gated ion channels, a diazirine derivative of the potent intravenous anesthetic, R-(+)-etomidate (2-ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate), has been synthesized and characterized. R-(+)-Azietomidate [2-(3-methyl-3H-diaziren-3-yl)ethyl 1-(l-phenylethyl)-1H-imidazole-5-carboxylate] anesthetizes tadpoles with an EC50 of 2.2 muM, identical to that of R-(+)-etomidate. At this concentration both agents equally enhanced GABA-induced currents and decreased binding of the caged-convulsant [S-35]TBPS to GABA(A) receptors. In all of the above actions R-(+)-azietomidate is about an order of magnitude more potent than S-(-)-azietomidate, an enantioselectivity comparable to etomidate's. R-(+)-Azietomidate also inhibits acetylcholine-induced currents in nicotinic acetylcholine receptors, with about twice the potency of the parent compound. [H-3]Azietomidate photoincorporated into Torpedo nicotinic acetylcholine receptor-rich membranes. Desensitization decreased photoincorporation into the delta-subunit and increased that into the alpha-subunit. The latter increase was confined to a proteolytic fragment containing the first three transmembrane segments. Thus, R-(+)-azietomidate is a potent stereoselective general anesthetic and an effective photolabel.