tert-butyl N-[(2S)-1-[(1S,4R,7R,10S)-4,7-dibenzyl-3,6,9-trioxo-2,5,8,11-tetrazabicyclo[8.2.1]tridecan-11-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate | 1400442-92-3

• 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 N-[(2S)-1-[(1S,4R,7R,10S)-4,7-dibenzyl-3,6,9-trioxo-2,5,8,11-tetrazabicyclo[8.2.1]tridecan-11-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate
• CAS: 1400442-92-3
• 化学式: C₃₇H₄₃N₅O₇
• 分子量: 669.778
• InChiKey: YGMBKQDMOOTNPS-XUIYDDGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  49
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  166
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[(2S)-1-[(1S,4R,7R,10S)-4,7-dibenzyl-3,6,9-trioxo-2,5,8,11-tetrazabicyclo[8.2.1]tridecan-11-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 3.0h， 以93%的产率得到(1S,4R,7R,10S)-11-[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]-4,7-dibenzyl-2,5,8,11-tetrazabicyclo[8.2.1]tridecane-3,6,9-trione;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  cis-4-Amino-l-proline Residue As a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues: Part 2

  摘要：

  Recently, we reported synthesis and activity of a constrained cyclic analogue of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) and related linear models containing the cis-4-amino-L-proline (cAmp) in place of native Pro(2). In the present article, the adopted rationale is the possible modulation of the receptor affinity of the cAmp containing EM-2 analogues by assigning a different stereochemistry to the Phe(3) and Phe(4) residues present in the ring. Thus, eight more analogues with different absolute configuration at the chiral center of the aromatic residues in positions 3 and 4 have been synthesized and their opioid activity examined. The stereochemical change at the alpha-carbon atoms leads to a meaningful enhancement of the affinity and activity toward mu opioid receptors with respect to the prototype compound 9: e.g., 9a, K-i(mu) = 63 nM, GPI (IC50) = 480 nM; 9b, K-i(mu) = 38 nM, GPI (IC50) = 330 nM.

  DOI：

  10.1021/jm300947s
• 作为产物：
  描述：

  Boc-D-Phe-D-Phe-OMe 在 N-甲基吗啉 、 palladium 10% on activated carbon 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 tert-butyl N-[(2S)-1-[(1S,4R,7R,10S)-4,7-dibenzyl-3,6,9-trioxo-2,5,8,11-tetrazabicyclo[8.2.1]tridecan-11-yl]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate
  参考文献：
  名称：

  cis-4-Amino-l-proline Residue As a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues: Part 2

  摘要：

  Recently, we reported synthesis and activity of a constrained cyclic analogue of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) and related linear models containing the cis-4-amino-L-proline (cAmp) in place of native Pro(2). In the present article, the adopted rationale is the possible modulation of the receptor affinity of the cAmp containing EM-2 analogues by assigning a different stereochemistry to the Phe(3) and Phe(4) residues present in the ring. Thus, eight more analogues with different absolute configuration at the chiral center of the aromatic residues in positions 3 and 4 have been synthesized and their opioid activity examined. The stereochemical change at the alpha-carbon atoms leads to a meaningful enhancement of the affinity and activity toward mu opioid receptors with respect to the prototype compound 9: e.g., 9a, K-i(mu) = 63 nM, GPI (IC50) = 480 nM; 9b, K-i(mu) = 38 nM, GPI (IC50) = 330 nM.

  DOI：

  10.1021/jm300947s

文献信息

• <i>cis</i>-4-Amino-<scp>l</scp>-proline Residue As a Scaffold for the Synthesis of Cyclic and Linear Endomorphin-2 Analogues: Part 2
  作者：Adriano Mollica、Francesco Pinnen、Azzurra Stefanucci、Luisa Mannina、Anatoly P. Sobolev、Gino Lucente、Peg Davis、Josephine Lai、Shou-Wu Ma、Frank Porreca、Victor J. Hruby

  DOI：10.1021/jm300947s

  日期：2012.10.11

  Recently, we reported synthesis and activity of a constrained cyclic analogue of endomorphin-2 (EM-2: Tyr-Pro-Phe-Phe-NH2) and related linear models containing the cis-4-amino-L-proline (cAmp) in place of native Pro(2). In the present article, the adopted rationale is the possible modulation of the receptor affinity of the cAmp containing EM-2 analogues by assigning a different stereochemistry to the Phe(3) and Phe(4) residues present in the ring. Thus, eight more analogues with different absolute configuration at the chiral center of the aromatic residues in positions 3 and 4 have been synthesized and their opioid activity examined. The stereochemical change at the alpha-carbon atoms leads to a meaningful enhancement of the affinity and activity toward mu opioid receptors with respect to the prototype compound 9: e.g., 9a, K-i(mu) = 63 nM, GPI (IC50) = 480 nM; 9b, K-i(mu) = 38 nM, GPI (IC50) = 330 nM.