1-(tert-butoxycarbonyl)-5-((2S)-4-carboxymethyl-7-nitro-3-oxo-2,3,4,5-tetrahydro-1H-benzo[1,4]diazepin-2-ylmethyl)imidazole | 669772-31-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 1-(tert-butoxycarbonyl)-5-((2S)-4-carboxymethyl-7-nitro-3-oxo-2,3,4,5-tetrahydro-1H-benzo[1,4]diazepin-2-ylmethyl)imidazole
• CAS: 669772-31-0
• 化学式: C₂₀H₂₃N₅O₇
• 分子量: 445.432
• InChiKey: QTJUKEIKRVGHMG-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  156.9
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  1-(tert-butoxycarbonyl)-5-((2S)-4-carboxymethyl-7-nitro-3-oxo-2,3,4,5-tetrahydro-1H-benzo[1,4]diazepin-2-ylmethyl)imidazole 在 palladium on activated charcoal 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 5-((S)-7-Amino-4-carboxymethyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-ylmethyl)-imidazole-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  A Selective AT₂ Receptor Ligand with a γ-Turn-Like Mimetic Replacing the Amino Acid Residues 4−5 of Angiotensin II

  摘要：

  Three angiotensin II (Ang II) analogues encompassing a benzodiazepine-based gamma-turn-like scaffold have been synthesized. Evaluation of the compounds in a radioligand binding assay showed that they had no affinity to the rat liver AT(1) receptor. However, one of the compounds displayed considerable affinity to the pig uterus AT(2) receptor (K-i = 3.0 nM) while the other two lacked affinity to this receptor. It was hypothesized that the reason for the inactivity of one of these analogues to the AT(2) receptor was that the guanidino group of the Arg(2) residue and/or the N-terminal end of the pseudopeptide could not interact optimally with the receptor. To investigate this hypothesis, a conformational analysis was performed and a comparison was carried out with the monocyclic methylenedithioether analogue cyclo(S-CH2-S) [CyS3,5]-Ang II which is known to bind with high affinity to the AT(2) receptor (K-i = 0.62 nM). This comparison showed that, in the compounds with high AT(2) receptor affinity, the guanidino group of the Arg(2) residue and the N-terminal end could access common regions of space that were not accessible to the inactive compound. To examine the importance of the guanidino group for binding, the Arg side chain was removed by substituting Arg(2) for Ala(2) in the analogue having the high affinity. This analogue lacked affinity to AT(2) receptors, which supports the role of the guanidino group in receptor binding.

  DOI：

  10.1021/jm030921v
• 作为产物：
  描述：

  [2-(tert-butyldiphenylsilanyloxy)ethyl]-(2-fluoro-5-nitrobenzyl)amine 在 sodium chlorite 、 sodium dihydrogenphosphate 、 草酰氯 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 环己烯 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 二甲基亚砜 、 叔丁醇 为溶剂， 反应 75.83h， 生成 1-(tert-butoxycarbonyl)-5-((2S)-4-carboxymethyl-7-nitro-3-oxo-2,3,4,5-tetrahydro-1H-benzo[1,4]diazepin-2-ylmethyl)imidazole
  参考文献：
  名称：

  A Selective AT₂ Receptor Ligand with a γ-Turn-Like Mimetic Replacing the Amino Acid Residues 4−5 of Angiotensin II

  摘要：

  Three angiotensin II (Ang II) analogues encompassing a benzodiazepine-based gamma-turn-like scaffold have been synthesized. Evaluation of the compounds in a radioligand binding assay showed that they had no affinity to the rat liver AT(1) receptor. However, one of the compounds displayed considerable affinity to the pig uterus AT(2) receptor (K-i = 3.0 nM) while the other two lacked affinity to this receptor. It was hypothesized that the reason for the inactivity of one of these analogues to the AT(2) receptor was that the guanidino group of the Arg(2) residue and/or the N-terminal end of the pseudopeptide could not interact optimally with the receptor. To investigate this hypothesis, a conformational analysis was performed and a comparison was carried out with the monocyclic methylenedithioether analogue cyclo(S-CH2-S) [CyS3,5]-Ang II which is known to bind with high affinity to the AT(2) receptor (K-i = 0.62 nM). This comparison showed that, in the compounds with high AT(2) receptor affinity, the guanidino group of the Arg(2) residue and the N-terminal end could access common regions of space that were not accessible to the inactive compound. To examine the importance of the guanidino group for binding, the Arg side chain was removed by substituting Arg(2) for Ala(2) in the analogue having the high affinity. This analogue lacked affinity to AT(2) receptors, which supports the role of the guanidino group in receptor binding.

  DOI：

  10.1021/jm030921v