tert-butyl (RS)-2-(N,N-di-tert-butoxycarbonylamino)-3-[3-isopropoxy-5(1H-5-tetrazolyl)-4-isoxazolyl]propionate | 852567-86-3

• 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: tert-butyl (RS)-2-(N,N-di-tert-butoxycarbonylamino)-3-[3-isopropoxy-5(1H-5-tetrazolyl)-4-isoxazolyl]propionate
• 英文别名: tert-butyl (RS)-2-(N,N-di-tert-butoxycarbonylamino)-3-[3-isopropoxy-5-(1H-5-tetrazoyl)-4-isoxazolyl]propionate；tert-butyl 2-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-[3-propan-2-yloxy-5-(2H-tetrazol-5-yl)-1,2-oxazol-4-yl]propanoate
• CAS: 852567-86-3
• 化学式: C₂₄H₃₈N₆O₈
• 分子量: 538.601
• InChiKey: RCJZBVIGBCHEGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  172
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  tert-butyl (RS)-2-(N,N-di-tert-butoxycarbonylamino)-3-[3-isopropoxy-5(1H-5-tetrazolyl)-4-isoxazolyl]propionate 在 氢溴酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 0.33h， 生成 2-Amino-3-[3-hydroxy-5-(1-propyl-1H-tetrazol-5-yl)-isoxazol-4-yl]-propionic acid
  参考文献：
  名称：

  Convergent Synthesis and Pharmacology of Substituted Tetrazolyl-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid Analogues

  摘要：

  The synthesis and pharmacological characterization of 1- and 2-alkyltetrazolyl analogues of (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA), a highly potent and selective agonist at AMPA receptors, are presented. A shorter and more convergent synthetic route than previously described, employing a new method for introducing the amino acid moiety, was developed for these derivatives. The 2-substituted isomers were selective agonists, and their activity correlated inversely with the size of the substituent. Structural explanations of the structure-activity relationship are provided.

  DOI：

  10.1021/jm050014l
• 作为产物：
  描述：

  methyl 3-isopropoxyisoxazole-5-carboxylate 在 ammonium hydroxide 、 正丁基锂 、 sodium azide 、 三乙胺盐酸盐 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 74.33h， 生成 tert-butyl (RS)-2-(N,N-di-tert-butoxycarbonylamino)-3-[3-isopropoxy-5(1H-5-tetrazolyl)-4-isoxazolyl]propionate
  参考文献：
  名称：

  Convergent Synthesis and Pharmacology of Substituted Tetrazolyl-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid Analogues

  摘要：

  The synthesis and pharmacological characterization of 1- and 2-alkyltetrazolyl analogues of (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA), a highly potent and selective agonist at AMPA receptors, are presented. A shorter and more convergent synthetic route than previously described, employing a new method for introducing the amino acid moiety, was developed for these derivatives. The 2-substituted isomers were selective agonists, and their activity correlated inversely with the size of the substituent. Structural explanations of the structure-activity relationship are provided.

  DOI：

  10.1021/jm050014l

文献信息

• A Tetrazolyl-Substituted Subtype-Selective AMPA Receptor Agonist
  作者：Stine B. Vogensen、Karla Frydenvang、Jeremy R. Greenwood、Giovanna Postorino、Birgitte Nielsen、Darryl S. Pickering、Bjarke Ebert、Ulrik Bølcho、Jan Egebjerg、Michael Gajhede、Jette S. Kastrup、Tommy N. Johansen、Rasmus P. Clausen、Povl Krogsgaard-Larsen

  DOI：10.1021/jm061439q

  日期：2007.5.1

  Replacement of the methyl group of the AMPA receptor agonist 2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA) with a benzyl group provided the first AMPA receptor agonist, compound 7, capable of discriminating GluR2-4 from GluR1 by its more than 10-fold preference for the former receptor subtypes. An X-ray crystallographic analysis of this new analogue in

  AMPA受体激动剂2-氨基-3- [3-羟基-5-（2-甲基-2H-5-四唑基）-4-异恶唑基]丙酸（2-Me-​​Tet-AMPA）的甲基取代带有苄基的化合物提供了第一种AMPA受体激动剂化合物7，该化合物能够以比先前受体亚型高10倍以上的偏好来将GluR2-4与GluR1区分开。对该新类似物与GluR2-S1S2J构建体的复合物的X射线晶体学分析表明，苄基基团的容纳在受体中产生了以前未观察到的口袋，这可能解释了化合物7的显着药理特性。
• Convergent Synthesis and Pharmacology of Substituted Tetrazolyl-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid Analogues
  作者：Stine B. Vogensen、Rasmus P. Clausen、Jeremy R. Greenwood、Tommy N. Johansen、Darryl S. Pickering、Birgitte Nielsen、Bjarke Ebert、Povl Krogsgaard-Larsen

  DOI：10.1021/jm050014l

  日期：2005.5.1

  The synthesis and pharmacological characterization of 1- and 2-alkyltetrazolyl analogues of (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA), a highly potent and selective agonist at AMPA receptors, are presented. A shorter and more convergent synthetic route than previously described, employing a new method for introducing the amino acid moiety, was developed for these derivatives. The 2-substituted isomers were selective agonists, and their activity correlated inversely with the size of the substituent. Structural explanations of the structure-activity relationship are provided.