7'-aminonaltrindole | 143619-57-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 7'-aminonaltrindole
• 英文别名: (1S,2S,13R,21R)-9-amino-22-(cyclopropylmethyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15,17,19(25)-heptaene-2,16-diol
• CAS: 143619-57-2
• 化学式: C₂₆H₂₇N₃O₃
• 分子量: 429.519
• InChiKey: YDHSNDRGEGRWED-UAZYKBCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  94.7
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7'-aminonaltrindole 在 potassium carbonate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 121.0h， 生成 N-[(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2,16-dihydroxy-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15,17,19(25)-heptaen-9-yl]benzamide
  参考文献：
  名称：

  荧光亲和标记7'-（邻苯二甲醛甲酰胺基）纳丁三醇（PNTI）共价诱导δ阿片受体激活。

  摘要：

  DOI：

  10.1021/jm010004u
• 作为产物：
  描述：

  盐酸纳曲酮 在 盐酸 、 5% Pd/C 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 90.0 ℃ 、275.8 kPa 条件下， 反应 4.0h， 生成 7'-aminonaltrindole
  参考文献：
  名称：

  Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers

  摘要：

  Opioid receptors, including the mu- and delta-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.

  DOI：

  10.1021/ml300083p

文献信息

• NOVEL MORPHINE DERIVATIVES
  申请人：Larbouret Karine

  公开号：US20100075912A1

  公开（公告）日：2010-03-25

  The present invention relates to new morphine-6-glucuronide derivatives, to pharmaceutical compositions thereof and uses thereof.

  本发明涉及新的吗啡-6-葡糖醛酸酯衍生物，其药用组合物及其用途。
• <i>o</i>-Naphthalenedicarboxaldehyde Derivative of 7‘-Aminonaltrindole as a Selective δ-Opioid Receptor Affinity Label
  作者：Sarika Prabhu Haris、Yan Zhang、Bertrand Le Bourdonnec、Christopher R. McCurdy、Philip S. Portoghese

  DOI：10.1021/jm061194h

  日期：2007.7.1

  Incorporation of a naphthalene-dialdehyde moiety into the delta antagonist, 6'-aminonaltrindole afforded a potent, selective, irreversible delta-agonist 1. However, flow cytometry studies revealed no time-dependent specific fluorescence, suggesting that both Lys214 and Cys216 at the recognition site are not involved in covalent binding. Molecular simulation studies suggest that compound 1 may form a Schiff base with the epsilon-amino group of Lys214, which could explain its irreversibility and transformation into a delta-agonist through a conformational change of TM5.
• A Bivalent Ligand (KDN-21) Reveals Spinal δ and κ Opioid Receptors Are Organized as Heterodimers That Give Rise to δ₁ and <i>κ</i>₂ Phenotypes. Selective Targeting of δ−κ Heterodimers
  作者：Rashmi G. Bhushan、Shiv K. Sharma、Zhihua Xie、David J. Daniels、Philip S. Portoghese

  DOI：10.1021/jm0342358

  日期：2004.6.1

  In view of recent pharmacological studies suggesting the existence of delta-kappa opioid receptor heterodimers/oligomers in the spinal cord, we have synthesized and evaluated (intrathecally in mice) a series of bivalent ligands (KDN series) containing kappa and delta antagonist pharmacophores. Pharmacological and binding data have provided evidence for the bridging of spinal delta-kappa receptor heterodimers by KDN-21 and for their identification as delta(1) and kappa(2). The selectivity profile of KDN-21 and the apparent absence of coupled delta(1)-kappa(2) phenotypes in the brain suggest a new approach for targeting receptors.
• .delta. Opioid antagonist activity and binding studies of regioisomeric isothiocyanate derivatives of naltrindole: evidence for .delta. receptor subtypes
  作者：P. S. Portoghese、M. Sultana、W. L. Nelson、P. Klein、A. E. Takemori

  DOI：10.1021/jm00100a014

  日期：1992.10

  The isothiocyanate group was attached to the 4'-, 5'-, 6'-, or 7'-position of naltrindole in an effort to determine the importance of the position of this electrophilic group on the selectivity for subtypes of delta opioid receptors. All of the ligands were delta-selective when tested against standard agonists in smooth muscle preparations. However, the rank-order delta antagonism of antinociception in mice did not parallel the in vitro pharmacologic data. The 5'-isothiocyanate 2 was the most potent and selective antagonist in vivo, causing a 52-fold increase of the ED50 for [D-Ser2,D-Leu5]enkephalin-Thr6 (DSLET) and no increase for [D-Pen2,D-Pen5]enkephalin (DPDPE). The effect of each of the ligands on the binding of [H-3]DSLET and [H-3]DPDPE to guinea pig brain membranes clearly differentiated between the binding sites that recognize these radioligands. These studies provide additional evidence for the presence of two subtypes of delta opioid receptors.
• Transformation of a κ-Opioid Receptor Antagonist to a κ-Agonist by Transfer of a Guanidinium Group from the 5‘- to 6‘-Position of Naltrindole
  作者：Shiv Kumar Sharma、Robert M. Jones、Thomas G. Metzger、David M. Ferguson、Philip S. Portoghese

  DOI：10.1021/jm010095v

  日期：2001.6.1

  The importance of the indole scaffold of GNTI 3 in directing its address (5'-guanidinium group) to associate with the Glu297 residue of the Ic-opioid receptor was investigated by the synthesis and biological evaluation of its 4'- (4a), 6'- (4b), and 7'- (4c) regioisomers. The finding that only the 5'-regioisomer (GNTI) possessed potent K-opioid antagonist activity and high affinity at K-receptors illustrates the importance of the 5'-position in orienting the guanidinium group to the proper recognition locus (Glu 297) for potent K-antagonist activity. The discovery that the 6'-regioisomer of GNTI was a potent K-agonist, together with the results of site-directed mutagenesis studies that are consistent with association between the 6'-guanidinium group and Glu297, suggest that the transition from an inactive to an active state of the,c-receptor involves a conformational change of TM6. We propose that association of the 6'-guanidinium group of 4b with Glu297 promotes axial rotational motion of transmembrane helix VI which leads to receptor activation via a conformational change of inner loop 3.