5'-aminoethyl-17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3,14-dihydroxyindolo[2',3':6,7]morphinan | 288621-59-0

• 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: 5'-aminoethyl-17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3,14-dihydroxyindolo[2',3':6,7]morphinan
• 英文别名: (1S,2S,13R,21R)-7-(2-aminoethyl)-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: 288621-59-0
• 化学式: C₂₈H₃₁N₃O₃
• 分子量: 457.572
• InChiKey: ZYESGPQRGYSCFE-CSZVXOJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  5'-aminoethyl-17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3,14-dihydroxyindolo[2',3':6,7]morphinan 在 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 17.0h， 生成 17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-5'-(N-ethyl-N'-ethylurea)-3,14-dihydroxyindolo[2',3':6,7]morphinan
  参考文献：
  名称：

  The Role of the Side Chain in Determining Relative δ- and κ-Affinity in C5‘-Substituted Analogues of Naltrindole

  摘要：

  The role of the side chain in 5'-substituted analogues of naltrindole has been further explored with the synthesis of series of amides, amidines, and ureas. Amidines (8, 13) had greatest selectivity for the kappa receptor, as predicted from consideration of the message-address concept. It was also found that an appropriately located carbonyl group, in ureas (10) and amides (7), led to retention of affinity and antagonist potency at the 6 receptor.

  DOI：

  10.1021/jm020997b
• 作为产物：
  描述：

  盐酸纳曲酮 在 镍 盐酸 、 ammonium hydroxide 、 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 80.0~95.0 ℃ 、517.12 kPa 条件下， 反应 80.0h， 生成 5'-aminoethyl-17-cyclopropylmethyl-6,7-didehydro-4,5α-epoxy-3,14-dihydroxyindolo[2',3':6,7]morphinan
  参考文献：
  名称：

  κ阿片受体的有效和选择性吲哚吗啡拮抗剂。

  摘要：

  δ-阿片样物质拮抗剂纳曲酮（2，NTI）中的吲哚部分被用作支架，以保持与κ-阿片样物质受体相互作用的“地址”。地址与吲哚部分5'-位的连接是基于NTI在κ拮抗剂降冰片碱（1，norBNI）上的叠加。为了研究其与κ受体上的阴离子地址亚位Glu297的相互作用，采用了各种阳离子基团作为κ地址。用于该目的的一些基团是胺，am，胍和季铵。在平滑肌制剂中进行测试时，发现该系列成员具有​​不同程度的kappa拮抗剂效力和kappa选择性。5' -胍衍生物12a（GNTI）是该系列中最有效的成员，并且具有最高的κ选择性比。GNTI的效力是norBNI的2倍，选择性高6-10倍（1）。通常，该系列中效力的顺序是：胍> approximately近似为季铵>胺。κ拮抗剂效力似乎是pK（a）和配体阳离子取代基的距离限制的组合的函数。受体结合研究在质量上与药理学数据一致。对12a的分子建模研究表明，GNTI的质

  DOI：

  10.1021/jm0000665

文献信息

• Guanidino N-Substituted and N,N-Disubstituted Derivatives of the κ-Opioid Antagonist GNTI
  作者：Shannon L. Black、Cedric Chauvignac、Peter Grundt、Carl N. Miller、Susan Wood、John R. Traynor、John W. Lewis、Stephen M. Husbands

  DOI：10.1021/jm0309203

  日期：2003.12.1

  Derivatives of the highly selective kappa-opioid receptor antagonist GNTI (2a) have been prepared. Binding and functional studies conducted on cloned human opioid receptors expressed in Chinese hamster ovarian (CHO) cells suggested that adding a benzyl or a substituted benzyl group to the guanidino moiety led, in general, to a retention of high kappa-affinity and antagonist potency. Disubstitution of the guanidino moiety led to reduced kappa-selectivity.
• Selective κ-opioid antagonists related to naltrindole. effect of side-chain spacer in the 5′-amidinoalkyl series
  作者：Andrew R Jales、Stephen M Husbands、John W Lewis

  DOI：10.1016/s0960-894x(00)00433-9

  日期：2000.10

  The study of kappa -opioid receptor function in vivo has been hampered by the limited choice of selective kappa -antagonists. Recently discovered cc-antagonists have not yet been utilised in vivo. We here report the synthesis and in vitro evaluation of a new amidine derivative of naltrindole. It showed substantially greater kappa -selectivity in binding assays than known analogues with shorter spacer in the amidine side chain. This indicates that in nor-BNI and related selective kappa -antagonists, the second basic centre may not be ideally located. (C) 2000 Elsevier Science Ltd. All rights reserved.
• The Role of the Side Chain in Determining Relative δ- and κ-Affinity in C5‘-Substituted Analogues of Naltrindole
  作者：Shannon L. Black、Andrew R. Jales、Wolfgang Brandt、John W. Lewis、Stephen M. Husbands

  DOI：10.1021/jm020997b

  日期：2003.1.1

  The role of the side chain in 5'-substituted analogues of naltrindole has been further explored with the synthesis of series of amides, amidines, and ureas. Amidines (8, 13) had greatest selectivity for the kappa receptor, as predicted from consideration of the message-address concept. It was also found that an appropriately located carbonyl group, in ureas (10) and amides (7), led to retention of affinity and antagonist potency at the 6 receptor.
• Potent and Selective Indolomorphinan Antagonists of the Kappa-Opioid Receptor
  作者：William C. Stevens、Robert M. Jones、Govindan Subramanian、Thomas G. Metzger、David M. Ferguson、Philip S. Portoghese

  DOI：10.1021/jm0000665

  日期：2000.7.1

  the kappa antagonist, norbinaltorphimine (1, norBNI). A variety of cationic groups were employed as a kappa address in an effort to investigate its interaction with the anionic address subsite, Glu297, on the kappa receptor. Some of the groups that were employed for this purpose were amines, amidines, guanidines, and quaternary ammonium. Members of the series were found to have a varying degree of kappa

  δ-阿片样物质拮抗剂纳曲酮（2，NTI）中的吲哚部分被用作支架，以保持与κ-阿片样物质受体相互作用的“地址”。地址与吲哚部分5'-位的连接是基于NTI在κ拮抗剂降冰片碱（1，norBNI）上的叠加。为了研究其与κ受体上的阴离子地址亚位Glu297的相互作用，采用了各种阳离子基团作为κ地址。用于该目的的一些基团是胺，am，胍和季铵。在平滑肌制剂中进行测试时，发现该系列成员具有​​不同程度的kappa拮抗剂效力和kappa选择性。5' -胍衍生物12a（GNTI）是该系列中最有效的成员，并且具有最高的κ选择性比。GNTI的效力是norBNI的2倍，选择性高6-10倍（1）。通常，该系列中效力的顺序是：胍> approximately近似为季铵>胺。κ拮抗剂效力似乎是pK（a）和配体阳离子取代基的距离限制的组合的函数。受体结合研究在质量上与药理学数据一致。对12a的分子建模研究表明，GNTI的质