N-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethyl]-3,4-bis(1,3-dioxolan-2-yl)benzamide | 1054312-54-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: N-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethyl]-3,4-bis(1,3-dioxolan-2-yl)benzamide
• CAS: 1054312-54-7
• 化学式: C₃₅H₄₁N₃O₉
• 分子量: 647.725
• InChiKey: UWVSGCIACCSFTK-GMDWMDBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  47
• 可旋转键数：
  8
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethyl]-3,4-bis(1,3-dioxolan-2-yl)benzamide 在 盐酸 作用下， 以 丙酮 为溶剂， 反应 168.0h， 以38%的产率得到N-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethyl]-3,4-diformylbenzamide
  参考文献：
  名称：

  Affinity labels as tools for the identification of opioid receptor recognition sites

  摘要：

  Affinity labels have proven to be useful tools in opioid research. We review experiments carried out with the mu opioid receptor affinity label, beta-funaltrexamine (2), that support the concept of different recognition sites for mu opioid agonists and antagonists. The data are interpreted in the context of a dimeric receptor that contains two allosterically coupled binding sites: one that binds endogenous agonist, and the second that functions as an inhibitory modulator of agonism. It is proposed that exogenous antagonists bind selectively to the second site. The first of a new class of affinity labels, PGNA (5), that contains the phthaldehyde moiety attached to an opioid antagonist pharmacophore, is described. This class of ligands has been named 'reporter affinity labels' because covalent association leads to the formation of a fluorescent isoindole that is diagnostic for cross-linking of lysine and cysteine residues. PGNA binds opioid receptors covalently, as suggested by (a) irreversible binding to cloned opioid receptors, (b) irreversible opioid antagonism in the guinea-pig ileum preparation, and (c) ultra-long opioid antagonism in mice. Since flow cytometry experiments revealed specific enhancement of fluorescence in cloned mu receptors after a 1 min exposure to 5, it is concluded that covalent binding has occurred via the formation of an isoindole, presumably by cross-linking neighboring lysine and cysteine residues in the vicinity of the receptor recognition site. (C) 2001 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01040-0
• 作为产物：
  描述：

  3,4-双(二溴甲基)苯甲酸 在 sodium hydroxide 、 sodium carbonate 、 1-羟基苯并三唑 、 对甲苯磺酸 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 46.0h， 生成 N-[2-[[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethyl]-3,4-bis(1,3-dioxolan-2-yl)benzamide
  参考文献：
  名称：

  Affinity labels as tools for the identification of opioid receptor recognition sites

  摘要：

  Affinity labels have proven to be useful tools in opioid research. We review experiments carried out with the mu opioid receptor affinity label, beta-funaltrexamine (2), that support the concept of different recognition sites for mu opioid agonists and antagonists. The data are interpreted in the context of a dimeric receptor that contains two allosterically coupled binding sites: one that binds endogenous agonist, and the second that functions as an inhibitory modulator of agonism. It is proposed that exogenous antagonists bind selectively to the second site. The first of a new class of affinity labels, PGNA (5), that contains the phthaldehyde moiety attached to an opioid antagonist pharmacophore, is described. This class of ligands has been named 'reporter affinity labels' because covalent association leads to the formation of a fluorescent isoindole that is diagnostic for cross-linking of lysine and cysteine residues. PGNA binds opioid receptors covalently, as suggested by (a) irreversible binding to cloned opioid receptors, (b) irreversible opioid antagonism in the guinea-pig ileum preparation, and (c) ultra-long opioid antagonism in mice. Since flow cytometry experiments revealed specific enhancement of fluorescence in cloned mu receptors after a 1 min exposure to 5, it is concluded that covalent binding has occurred via the formation of an isoindole, presumably by cross-linking neighboring lysine and cysteine residues in the vicinity of the receptor recognition site. (C) 2001 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0014-827x(01)01040-0

文献信息

• Reporter Affinity Labels:  An <i>o</i>-Phthalaldehyde Derivative of β-Naltrexamine as a Fluorogenic Ligand for Opioid Receptors
  作者：Bertrand Le Bourdonnec、Rachid El Kouhen、Mary M. Lunzer、Ping Y. Law、Horace H. Loh、Philip S. Portoghese

  DOI：10.1021/jm000138s

  日期：2000.6.1