(1S)-trans-2-azidocyclopentanecarboxylic acid ethyl ester | 143617-94-1

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: (1S)-trans-2-azidocyclopentanecarboxylic acid ethyl ester
• 英文别名: ethyl (1S,2S)-2-azidocyclopentane-1-carboxylate
• CAS: 143617-94-1
• 化学式: C₈H₁₃N₃O₂
• 分子量: 183.21
• InChiKey: ZKPUAFGVWPNRAC-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  40.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S)-trans-2-azidocyclopentanecarboxylic acid ethyl ester 在 palladium on activated charcoal lithium hydroxide 、 氢气 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 (1S,2s)-boc-2-氨基环戊烷羧酸
  参考文献：
  名称：

  Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29

  摘要：

  A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp-Phe-NH2, (1)] Were prepared in which the Met28-Gly29 dipeptide was replaced by omega-aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2-aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts.

  DOI：

  10.1021/jm00099a005
• 作为产物：
  描述：

  ethyl cis-(±)-2-hydroxycyclopentane-1-carboxylate 在 迭氮酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 苯 为溶剂， 反应 3.0h， 以63%的产率得到(1S)-trans-2-azidocyclopentanecarboxylic acid ethyl ester
  参考文献：
  名称：

  Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29

  摘要：

  A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp-Phe-NH2, (1)] Were prepared in which the Met28-Gly29 dipeptide was replaced by omega-aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2-aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts.

  DOI：

  10.1021/jm00099a005

文献信息

• Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29
  作者：Jefferson W. Tilley、Waleed Danho、Shian Jan Shiuey、Irina Kulesha、Joseph Swistok、Raymond Makofske、Joseph Michalewsky、Joseph Triscari、David Nelson

  DOI：10.1021/jm00099a005

  日期：1992.10

  A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp-Phe-NH2, (1)] Were prepared in which the Met28-Gly29 dipeptide was replaced by omega-aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2-aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts.