(E)-7-benzylidenenaltrexone | 153611-34-8

• 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: (E)-7-benzylidenenaltrexone
• 英文别名: 7(E)-Benzylidenenaltrexone；7-benzylidene-7-dehydronaltrexone；anti-7-benzylidenenaltrexone；7-benzylidene naltrexamine；7-benzylidenenaltrexone；(4R,4aS,6E,7aR,12bS)-6-benzylidene-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 153611-34-8
• 化学式: C₂₇H₂₇NO₄
• 分子量: 429.516
• InChiKey: WXOUFNFMPVMGFZ-BDQAUFNLSA-N

物化性质

• 沸点：
  661.2±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (E)-7-benzylidenenaltrexone 以 二氯甲烷 为溶剂， 以75%的产率得到7(Z)-Benzylidenenaltrexone
  参考文献：
  名称：

  (E)- and (Z)-7-Arylidenenaltrexones:  Synthesis and Opioid Receptor Radioligand Displacement Assays

  摘要：

  The E-isomer of 7-benzylidenenaltrexone (BNTX, la) was reported by Portoghese(1,2) as a highly selective delta-opioid antagonist. The corresponding Z-isomer Ib was not readily available through direct aldol condensation of naltrexone (6) with benzaldehyde, Using the photochemical methods employed by Lewis to isomerize cinnamamides,(3) we have obtained Z-isomer Ib in good yield from E-isomer la. A series of (E)- and (Z)-7-arylidenenaltrexone derivatives was prepared to study the effect of larger arylidene groups on opioid receptor affinity in this series. By aldol condensation of naltrexone (6) with benzaldehyde, 1-naphthaldehyde, 2-naphthaldehyde, 4-phenylbenzaldehyde, and 9-anthracaldehyde, the (E)-arylidenes were readily obtained. Photochemical isomerization afforded the corresponding Z-isomers. These compounds were evaluated via opioid receptor radioligand displacement assays. In these assays, the Z-isomers generally had higher affinity and were more delta-selective than the corresponding E-isomers. The (Z)-7-(1-naphthylidene)naltrexone (3b) showed the greatest selectivity (delta:mu ratio of 15) and highest affinity delta-binding (K-i = 0.7 nM). PM3 semiempirical geometry optimizations suggest a significant role for the orientation of the arylidene substituent in the binding affinity and delta-receptor selectivity. This work demonstrates that larger groups may be incorporated into the arylidene portion of the molecule with opioid receptor affinity being retained.

  DOI：

  10.1021/jm960573f
• 作为产物：
  描述：

  盐酸纳曲酮 、 苯甲醛 在 哌啶 作用下， 以 甲醇 为溶剂， 以99%的产率得到(E)-7-benzylidenenaltrexone
  参考文献：
  名称：

  δ阿片受体拮抗剂7-亚苄基纳曲酮衍生物的抗trichomonal活性

  摘要：

  从纳曲酮（1）合成了7-亚苄基纳曲酮（BNTX）衍生物2a–v，3a–c，13a–c和14a，并评估了其抗滴虫活性。结构-活性-关系研究发现，4-碘-BNTX（2g）表现出最高的活性（IC 50  = 10.5 µM），对阿片样物质受体的亲和力对阴道毛滴虫的抗滴虫活性的重要性较小。。带有迈克尔受体双键和酚羟基的吗啡喃骨架将是开发抗滴虫剂的特定模板。此外，BNTX衍生物的抗滴虫活性机制可能与标准药物甲硝唑不同。

  DOI：

  10.1016/j.bmc.2017.06.026

文献信息

• Synthesis, Opioid Receptor Binding, and Biological Activities of Naltrexone-Derived Pyrido- and Pyrimidomorphinans
  作者：Subramaniam Ananthan、Hollis S. Kezar、Ronald L. Carter、Surendra K. Saini、Kenner C. Rice、Jennifer L. Wells、Peg Davis、Heng Xu、Christina M. Dersch、Edward J. Bilsky、Frank Porreca、Richard B. Rothman

  DOI：10.1021/jm990039i

  日期：1999.9.1

  evaluated for binding and biological activity at the opioid receptors. The unsubstituted pyridine 6a displayed high affinities at opioid delta, mu, and kappa receptors with K(i) values of 0.78, 1.5, and 8.8 nM, respectively. Compound 6a was devoid of agonist activity in the mouse vas deferens (MVD) and guinea pig ileum (GPI) preparations but was found to display moderate to weak antagonist activity in the

  从纳曲酮合成了一系列吡啶基和嘧啶吗啡喃（6a-h和7a-g），并评估了对阿片受体的结合和生物活性。未取代的吡啶6a在阿片样物质δ，μ和κ受体上显示出高亲和力，其K（i）值分别为0.78、1.5和8.8 nM。化合物6a在小鼠输精管（MVD）和豚鼠回肠（GPI）制剂中没有激动剂活性，但在MVD和GPI中显示出中等至弱的拮抗剂活性，K（e）值为37和164 nM，分别。通常，嘧啶吗啡喃比吡啶对应物具有更低的结合力和δ受体结合选择性。在吡啶基和嘧啶吗啡喃骨架上结合芳基作为假定的δ地址模拟物，使配体在结合亲和力和内在活性方面具有显着差异。在6a的4'位置或7a的等效6'位置连接苯基会导致所有三个阿片受体的结合力显着降低，这表明在配体结合位点存在某种相似的空间约束，mu和kappa受体的表达 相反，在6a的5'-位引入苯基不会引起在δ受体上的结合亲和力的任何降低。与未取代的吡啶6a相比，5' -苯基
• Synthesis and stereochemical assignment of 7-arylidene and 7-heteroarylidene morphinan-6-ones
  作者：Yang Nan、Subhash P. Upadhyaya、Wei Xu、Kathrine E. Hughes、William J. Dunn、Ludwig Bauer、Hemendra N. Bhargava、George A. Doss

  DOI：10.1002/jhet.5570330231

  日期：1996.3

  4-fluorobenzaldehyde, 3-and 4-pyridinecarboxaldehyde and 1-methyl-2-imidazolecarboxaldehyde) using piperidine as a catalyst. In addition, (E)-7-benzylidenenaloxone was prepared by the previously published Claisen-Schmidt condensation using sodium hydroxide in methanol. The stereochemistry of these arylidene derivatives 3–9 was determined to be (E) by means of nuclear Overhauser enhancement experiments. The

  若干（ë）-7- arylidenenaltrexones通过的水的共沸蒸馏从纳曲酮的苯溶液和芳族醛（苯甲醛，4-氯和4-氟代苯甲醛，3-和4-吡啶甲醛和1-甲基合成2-咪唑甲甲醛），以哌啶为催化剂。另外，（E）-7-亚苄基纳洛酮是通过先前公开的使用甲醇中的氢氧化钠的Claisen-Schmidt缩合制备的。通过核Overhauser增强实验确定了这些亚芳基衍生物3–9的立体化学为（E）。的13（的C NMR谱ë） - 3-9 以氘代氯仿记录盐酸盐，以氘代二甲基亚砜记录盐酸盐。
• THERAPEUTIC OR PREVENTIVE AGENT FOR NAUSEA/VOMITING
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1522542A1

  公开（公告）日：2005-04-13

  The present invention provides a therapeutic or prophylactic agent for preventing nausea and vomiting. The agent includes a morphinan derivative represented by general formula (I): or a pharmacologically acceptable acid addition salt thereof as an active ingredient, (where R1 represents, for example, a cyclopropylmethyl group, R2 and R3 represent, for example, a hydroxy or methoxy group, R4 and R5 together form, for example, an -O- bond, R6 represents, for example, a hydrogen atom, Q represents a substituted or unsubstituted group represented by, for example, the following formula: where X represents, for example, NH or NMe). The compounds of the present invention can be widely used as medicines against vomiting caused by emetic drugs. In particular, the compounds of the present invention are useful as therapeutic or prophylactic agents for preventing nausea and vomiting caused by µ-agonists represented by morphine.

  本发明提供了一种用于预防恶心和呕吐的治疗或预防剂。该剂包括一种由通式（I）表示的吗啡样衍生物或其药理学上可接受的酸盐作为活性成分，（其中R1代表例如环丙基甲基基团，R2和R3代表例如羟基或甲氧基，R4和R5共同形成例如-O-键，R6代表例如氢原子，Q代表由以下式子表示的取代或未取代基团，其中X代表例如NH或NMe）。 本发明的化合物可广泛用作抗呕吐药物。特别是，本发明的化合物对于由吗啡类µ-受体激动剂引起的恶心和呕吐的治疗或预防剂非常有用。
• Therapeutic or preventive agent for nausea/vomiting
  申请人：Kawai Koji

  公开号：US20060052409A1

  公开（公告）日：2006-03-09

  A therapeutic or prophylactic agent for preventing nausea and vomiting is disclosed. The agent includes a morphinan derivative represented by general formula (I): or a pharmacologically acceptable acid addition salt thereof as an active ingredient. The compounds are useful as therapeutic or prophylactic agents for preventing nausea and vomiting caused by μ-agonists represented by, morphine.

  本发明揭示了一种用于预防恶心和呕吐的治疗或预防剂。该剂包括一种以通式（I）表示的吗啡类衍生物，或其药理学上可接受的酸加成盐作为活性成分。这些化合物可用作治疗或预防剂，用于预防由吗啡等μ-激动剂引起的恶心和呕吐。
• ANTITUSSIVE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0636371A1

  公开（公告）日：1995-02-01

  An antitussive containing a δ-opioid antagonist or a pharmacologically acceptable salt thereof as the active ingredient. It has a potent activity, does not give side effects such as impaired mentation, and can be administered perorally.

  一种含有δ-类阿片拮抗剂或其药理上可接受的盐作为活性成分的止咳药。它具有很强的活性，不会产生副作用（如精神受损），并且可以经口给药。