Win 53365 | 103609-26-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Win 53365
• 英文别名: (2-methyl-1-(2-morpholinoethyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone；WIN53365；2-Methyl-3-(1-naphthylcarbonyl)-1-[2-(4-morpholinyl)ethyl]-1H-indole；[2-Methyl-1-(2-morpholin-4-yl-ethyl)-1H-indol-3-yl]-naphthalen-1-yl-methanone；[2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-naphthalen-1-ylmethanone
• CAS: 103609-26-3
• 化学式: C₂₆H₂₆N₂O₂
• 分子量: 398.505
• InChiKey: MCYSYVGXDRTALC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Win 53365 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以24%的产率得到[6-Bromo-2-methyl-1-(2-morpholin-4-yl-ethyl)-1H-indol-3-yl]-naphthalen-1-yl-methanone
  参考文献：
  名称：

  Aminoalkylindoles: Structure-Activity Relationships of Novel Cannabinoid Mimetics

  摘要：

  Aminoalkylindoles (AAIs) are a novel series of cannabinoid receptor ligands. In this report we disclose the structural features of AAIs which are important for binding to this receptor as measured by inhibition of binding of [H-3]Win 55212-2 (5). Functional activity in the mouse vas deferens is also noted and used to distinguish agonists from potential antagonists. The key structural features for potent cannabinoid activity in this series are a bicyclic (naphthyl) substituent at the 3-position, a small (II) substituent at the 2-position, and an aminoethyl (morpholinoethyl) substituent at the 1-position. A 6-bromo analog, Win 54461 (31), has been identified as a potential cannabinoid receptor antagonist. Modeling experiments were done to develop a pharmacophore and also to compare AAI structures with those of classical cannabinoids. The fact that the cannabinoid AAIs arose out of work on a series of cyclooxygenase inhibitors makes sense now that an endogenous cannabinoid ligand has been identified which is a derivative of arachidonic acid. Because of their unique structures and physical properties, AAIs provide useful tools to study the structure and function of the cannabinoid receptor(s).

  DOI：

  10.1021/jm00016a013
• 作为产物：
  描述：

  1-萘甲酰氯 在 甲基溴化镁 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Win 53365
  参考文献：
  名称：

  Antinociceptive (aminoalkyl)indoles

  摘要：

  The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) ''alpha-methylation'' caused an increase in PG inhibitory potency, (2) the (R)-alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported ''active'' conformations of the aroyl and related aromatic acetic acid derivatives. The H-1 NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD. The evidence is summarized which suggests that this second antinociceptive mechanism is associated with binding to the recently characterized cannabinoid receptor.

  DOI：

  10.1021/jm00107a034

文献信息

• New class of potent ligands for the human peripheral cannabinoid receptor
  作者：Michel Gallant、Claude Dufresne、Yves Gareau、Daniel Guay、Yves Leblanc、Petpiboon Prasit、Chantal Rochette、Nicole Sawyer、Deborah M. Slipetz、Nathalie Tremblay、Kathleen M. Metters、Marc Labelle

  DOI：10.1016/0960-894x(96)00426-x

  日期：1996.10

  A new class of potent ligand for the human peripheral cannabinoid (hCB(2)) receptor is described. Two indole analogs 13 and 17 exhibited nanomolar potencies (K-i) with good selectivity for the hCB(2) receptor over the human central cannabinoid (hCB(1)) receptor. Copyright (C) 1996 Elsevier Science Ltd
• [3 + 2]-Annulations of <i>N</i>-Hydroxy Allenylamines with Nitrosoarenes: One-Pot Synthesis of Substituted Indole Products
  作者：Pankaj Sharma、Rai-Shung Liu

  DOI：10.1021/acs.orglett.5b03447

  日期：2016.2.5

  In the presence of O-2 and an IPrCuCl additive (5 mol %), [3 + 2]-annulation reactions of N-hydroxyaniline with nitrosobenzenes in cold toluene form isoxazolidin-5-ol derivatives. Heating the same reaction mixture with DBU in toluene affords highly functionalized indole products efficiently. This method provides short synthesis of several bioactive molecules including WIN 48098, WIN 53365, and JWH 015.
• BELL, MALCOLM R.;DAMBRA, THOMAS E.;KUMAR, VIRENDRA;EISSENSTAT, MICHAEL A.+, J. MED. CHEM., 34,(1991) N, C. 1099-1110
  作者：BELL, MALCOLM R.、DAMBRA, THOMAS E.、KUMAR, VIRENDRA、EISSENSTAT, MICHAEL A.+

  DOI：——

  日期：——
• ——
  作者：BELL M. R.

  DOI：——

  日期：——
• US4581354A
  申请人：——

  公开号：US4581354A

  公开（公告）日：1986-04-08