1-(2-(morpholin-4-yl)ethyl)-2-methyl-3-(naphth-1-ylcarbonyl)-7-methoxyindole

• 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: 1-(2-(morpholin-4-yl)ethyl)-2-methyl-3-(naphth-1-ylcarbonyl)-7-methoxyindole
• 英文别名: [7-Methoxy-2-methyl-1-(2-morpholin-4-yl-ethyl)-1H-indol-3-yl]-naphthalen-1-yl-methanone；[7-methoxy-2-methyl-1-(2-morpholin-4-ylethyl)indol-3-yl]-naphthalen-1-ylmethanone
• 化学式: C₂₇H₂₈N₂O₃
• 分子量: 428.531
• InChiKey: MTRFKNOYFXNZLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  43.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-萘甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 氯化亚砜 、 二氯乙基铝 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 1-(2-(morpholin-4-yl)ethyl)-2-methyl-3-(naphth-1-ylcarbonyl)-7-methoxyindole
  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

文献信息

• 3-ACYLINDOLES COMME AGONISTES DU RECEPTEUR CB2
  申请人：SANOFI-SYNTHELABO

  公开号：EP0833818B1

  公开（公告）日：2001-10-17
• US6013648A
  申请人：——

  公开号：US6013648A

  公开（公告）日：2000-01-11
• [EN] CB2 RECEPTOR AGONIST COMPOUNDS<br/>[FR] COMPOSES AGONISTES DU RECEPTEUR CB2
  申请人：SANOFI

  公开号：WO1997000860A1

  公开（公告）日：1997-01-09

  (EN) The use of human CB2 receptor-specific agonists of formula (I) or (I') for preparing immunomodulating drugs is disclosed. In formulae (I) and (I'), R1 is a group selected from -CH2CHR10NR6R11, -(CH2)2NR'6R'11, -CHR9CH2NR'6R'11, -(CH2)nZ and -COR8; R'1 is a -CH2CHR10NR6R11 or -(CH2)2NR'6R'11 group; R2 and R'2 are hydrogen, halogen or C1-4 alkyl; R3 is hydrogen, C1-4 alkyl or a group selected from -CH2CHR10NR6R11, -(CH2)2NR'6R'11 and -COR8; R'3 is a =CR6R8 group; R4 has one of the meanings given for R5 or is a -COR8 group; R5 is hydrogen, C1-4 alkyl, C1-4 alkoxy, a halogen atom, a CF3 group, an OCF3 group or C1-4 alkylthio; R'5 has one of the meanings given for R5 and is in the 5 or 6 position of the indene ring; R6 is hydrogen or C1-4 alkyl; R'6 is C1-4 alkyl; R7 has one of the meanings given for R5 or R7 and R9 together form a -Y-CH2- group attached to the indole ring in the 7 position by a group Y; R8 is phenyl substituted one to four times by a substituent selected from halogen, C1-4 alkyl or C1-4 alkoxy; a polycyclic ring selected from naphth-1-yl, naphth-2-yl, 1,2,3,4-tetrahydronaphth-1-yl, 1,2,3,4-tetrahydronaphth-5-yl, anthryl, benzofuryl, benzothien-2-yl, benzothien-3-yl, 2-, 3-, 4- or 8-quinolyl, said polycyclic rings optionally being substituted once or twice by a substituent selected from C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, halogen, cyano, hydroxyl, trifluoromethyl and imidazol-1-yl; R10 and R11 together are a group selected from -CH2-O-CH2-CR12R13- and -(CH2)p-CR12R13-, wherein the carbon atom substituted by R12 and R13 is attached to the nitrogen atom; R'11 is C1-4 alkyl; or R'11 and R'6, taken together with the nitrogen atom to which they are attached, form a group selected from morpholin-4-yl, thiomorpholin-4-yl, piperidin-1-yl and pyrolidin-1-yl; each of R12 and R13 is independently hydrogen or C1-4 alkyl; n is 2, 3, 4 or 5; p is 2 or 3; Z is a methyl group or a halogen atom; and Y is a methylene group or an oxygen atom.(FR) L'invention a pour objet l'utilisation des agonistes spécifiques du récepteur CB2 humain pour la préparation de médicaments immunomodulateurs de formules (I) ou (I'), dans lesquelles: R1 représente un groupe choisi parmi les groupes -CH2CHR10NR6R11; -(CH2)2NR'6R'11; -CHR9CH2NR'6R'11; -(CH2)nZ et -COR8; R'1 représente le groupe -CH2CHR10NR6R11 ou le groupe -(CH2)2NR'6R'11; R2 et R'2 représentent l'hydrogène, un halogène ou un (C1-C4)alkyle; R3 représente l'hydrogène, un (C1-C4)alkyle ou un groupe choisi parmi les groupes -CH2CHR10NR6R11; -(CH2)2NR'6R'11 et -COR8; R'3 représente le groupe =CR6R8; R4 a l'une des significations données pour R5 ou représente un groupe -COR8; R5 représente l'hydrogène, un (C1-C4)alkyle, un (C1-C4)alcoxy, un atome d'halogène, un groupe CF3, un groupe OCF3, un (C1-C4)alkylthio; R'5 a l'une des significations données pour R5 et est en position 5 ou 6 du cycle indène; R6 représente l'hydrogène ou un (C1-C4)alkyle; R'6 représente un (C1-C4)alkyle; R7 a l'une des significations données pour R5 ou bien R7 et R9 constituent ensemble un groupe -Y-CH2- lié au cycle indole en position 7 par le groupe Y; R8 représente un phényle substitué une à quatre fois par un substituant choisi parmi: un halogène, un (C1-C4)alkyle et un (C1-C4)alcoxy; un polycycle choisi parmi un napht-1-yle, un napht-2-yle, un 1,2,3,4-tétrahydronapht-1-yle, un 1,2,3,4-tétrahydronapht-5-yle, un anthryle, un benzofuryle, un benzothièn-2-yle, un benzothièn-3-yle, un 2-,3-,4-, ou 8-quinolyle, lesdits polycycles étant non substitués ou substitués une ou deux fois par un substituant choisi parmi: un (C1-C4)alkyle, un (C1-C4)alcoxy, un (C1-C4)alkylthio, un halogène, un cyano, un hydroxyle, un trifluorométhyle, et un imidazol-1-yle; R10 et R11 ensemble représentent un groupe choisi parmi les groupes -CH2-O-CH2-CR12R13- et -(CH2)p-CR12R13-, dans lesquels l'atome de carbone substitué par R12 et R13 est lié à l'atome d'azote; R'11 représente un (C1-C4)alkyle ou bien R'11 et R'6 constituent avec l'atome d'azote auquel ils sont liés un groupe choisi parmi les groupes morpholia-4-yle, thiomorpholin-4-yle; pipéridin-1-yle et pyrolidin-1-yle; R12 et R13 représentent chacun, indépendamment l'un de l'autre, l'hydrogène ou un (C1-C4)alkyle; n est 2,3,4 ou 5; p est 2 ou 3; Z représente le groupe méthyle ou un atome d'halogène; Y représente le groupe méthylène ou l'atome d'oxygène.
• Aminoalkylindoles: Structure-Activity Relationships of Novel Cannabinoid Mimetics
  作者：Michael A. Eissenstat、Malcolm R. Bell、Thomas E. D'Ambra、E. John Alexander、Sol J. Daum、James H. Ackerman、Monte D. Gruett、Virendra Kumar、Kimberly G. Estep

  DOI：10.1021/jm00016a013

  日期：1995.8

  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).