9,10-dihydroanthracene-9-carboxylic acid 1-azabicyclo[2.2.2]oct-3(R)-yl ester | 320348-10-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 9,10-dihydroanthracene-9-carboxylic acid 1-azabicyclo[2.2.2]oct-3(R)-yl ester
• 英文别名: [(3R)-1-azabicyclo[2.2.2]octan-3-yl] 9,10-dihydroanthracene-9-carboxylate
• CAS: 320348-10-5
• 化学式: C₂₂H₂₃NO₂
• 分子量: 333.43
• InChiKey: DCVFVRXNLHLACD-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

文献信息

• NOVEL QUINUCLIDINE DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
  申请人：ALMIRALL, S.A.

  公开号：US20150246026A1

  公开（公告）日：2015-09-03

  A compound according to formula (I) wherein z© is a phenyl ring, a C 4 to C 9 heteroaromatic compound containing one or more heteroatoms, or a naphthalenyl, 5,6,7,8-tetrahydronaphthalenyl or biphenyl group; R 1 , R 2 and R 3 each independently represent a hydrogen or halogen atom, or a hydroxy group, or a phenyl, —OR 4 , —SR 4 , —NR 4 R 5 , —NHCOR 4 , —CONR 4 R 5 , —CN, —NO 2 , —COOR 4 or —CF 3 group, or a straight or branched lower alkyl group which may optionally be substituted, for example, with a hydroxy or alcoxy group, wherein R 4 and R 5 each independently represent a hydrogen atom, straight or branched lower alkyl group, or together form an alicyclic ring; or R 1 and R 2 together form an aromatic, alicyclic or heterocyclic ring; n is an integer from 0 to 4; A represents a —CH 2 —, —CH═CR 6 , —CR 6 ═CH—, —CR 6 12 2 —, —CO—, —O—, —S—, —S(O)—, SO 2 or NR 6 — group, wherein R 6 and R 2 each independently represent a hydrogen atom, straight or branched lower alkyl group, or R 6 and 12 2 together form an alicyclic ring; m is an integer from 0 to 8; provided that when m=0, A is not —CH 2 —; p is an integer from 1 to 2 and the substitution in the azoniabicyclic ring may be in the 2,3 or 4 position including all possible configurations of the asymmetric carbons; B represents a group of formula (i) or (ii), wherein R 10 represents a hydrogen atom, a hydroxy or methyl group; and R 8 and R 9 each independently represents formulae (a), (b), (c), (d) and wherein R 11 represents a hydrogen or halogen atom, or a straight or branched lower alkyl group and Q represents a single bond, —CH 2 —, —CH 2 —CH 2 , —O—, —O—CH 2 —, —S—, —S—CH 2 — or —CH═CH—, and when (i) or (ii) contain a chiral centre they may represent either configuration; X represents a pharmaceutically acceptable anion of a mono or polyvalent acid, which shows high affinity for muscarinic M 3 receptors (Hm3).

  根据式(I)的化合物，其中z©是苯环，含有一个或多个杂原子的C4至C9杂芳环化合物，或者是萘基、5,6,7,8-四氢萘基或联苯基；R1、R2和R3分别独立表示氢原子或卤素原子，或羟基，或苯基，—OR4，—SR4，—NR4R5，—NHCOR4，—CONR4R5，—CN，—NO2，—COOR4或—CF3基团，或直链或支链低碳烷基基团，该基团可能被羟基或烷氧基取代，其中R4和R5分别独立表示氢原子，直链或支链低碳烷基基团，或者共同形成脂环；或者R1和R2共同形成芳香环、脂环或杂环；n是从0到4的整数；A表示—CH2—，—CH═CR6，—CR6═CH—，—CR6122—，—CO—，—O—，—S—，—S(O)—，SO2或NR6—基团，其中R6和R2分别独立表示氢原子，直链或支链低碳烷基基团，或者R6和122共同形成脂环；m是从0到8的整数；但当m=0时，A不是— —；p是从1到2的整数，而在azoniabicyclic环中的取代基可以在2,3或4位置，包括对不对称碳的所有可能构型；B表示式(i)或(ii)的基团，其中R10表示氢原子，羟基或甲基基团；而R8和R9分别表示式(a)，(b)，(c)，(d)，其中R11表示氢原子或卤素原子，或者直链或支链低碳烷基基团，Q表示单键，— —，— — ，—O—，—O— —，—S—，—S— —或—CH═CH—，当(i)或(ii)含有手性中心时，它们可以表示任一构型；X表示单价或多价酸的药用可接受阴离子，对M3胆碱能受体（Hm3）具有高亲和力。
• Quinuclidine derivatives and their use as muscarinic M3 receptor ligands
  申请人：——

  公开号：US20030055080A1

  公开（公告）日：2003-03-20

  A compound according to formula (I) 1 wherein: is a phenyl ring, a C 4 to C 9 heteroaromatic compound containing one or more heteroatoms, or a naphthalenyl, 5,6,7,8-tetrahydronaphthalenyl or biphenyl group; R 1 , R 2 and R 3 each independently represent a hydrogen or halogen atom, or a hydroxy group, or a phenyl, —OR 4 , —SR 4 , —NR 4 R 5 , —NHCOR 4 , —CONR 4 R 5 , —CN, —NO 2 , —COOR 4 or —CF 3 group, or a straight or branched lower alkyl group which may optionally be substituted, for example, with a hydroxy or alcoxy group, wherein R 4 and R 5 each independently represent a hydrogen atom, straight or branched lower alkyl group, or together form an alicyclic ring; or R 1 and R 2 together form an aromatic, alicyclic or heterocyclic ring; n is an integer from 0 to 4; A represents a —CH 2 —, —CH═CR 6 , —CR 6 =CH—, —CR 6 R 7 —, —CO—, —O—, —S—, —S(O)—, SO 2 or —NR 6 — group, wherein R 6 and R 7 each independently represent a hydrogen atom, straight or branched lower alkyl group, or R 6 and R 7 together form an alicyclic ring; m is an integer from 0 to 8; provided that when m= 0 , A is not —CH 2 —; p is an integer from 1 to 2 and the substitution in the azoniabicyclic ring may be in the 2, 3 or 4 position including all possible configurations of the asymmetric carbons; B represents a group of formula i) or ii): 2 wherein R 10 represents a hydrogen atom, a hydroxy or methyl group; and R 8 and R 9 each independently represents 3 wherein R 11 represents a hydrogen or halogen atom, or a straight or branched lower alkyl group and Q represents a single bond, —CH 2 —, —CH 2 —CH 2 —, —O—, —O—CH 2 —, —S—, —S—CH 2 — or —CH═CH—, and when i) or ii) contain a chiral centre they may represent either configuration; X represents a pharmaceutically acceptable anion of a mono or polyvalent acid, which shows high affinity for muscarinic M 3 receptors (Hm3).

  根据公式（I）1，其中：是苯环，含有一个或多个杂原子的C4至C9杂芳族化合物，或者是萘基、5,6,7,8-四氢萘基或联苯基；R1、R2和R3分别独立表示氢或卤素原子，或羟基，或苯基，—OR4，—SR4，—NR4R5，—NHCOR4，—CONR4R5，—CN，—NO2，—COOR4或—CF3基团，或直链或支链的较低烷基基团，该基团可以选择性地被取代，例如，取代物可以是羟基或醇基，其中R4和R5分别独立表示氢原子，直链或支链较低烷基基团，或者共同形成脂环；或R1和R2共同形成芳香族、脂环或杂环；n是从0到4的整数；A表示—CH2—，—CH═CR6，—CR6=CH—，—CR6R7—，—CO—，—O—，—S—，—S(O)—，SO2或—NR6—基团，其中R6和R7分别独立表示氢原子，直链或支链较低烷基基团，或R6和R7共同形成脂环；m是从0到8的整数；但是当m=0时，A不是— —；p是从1到2的整数，而在azoniabicyclic环中的取代物可以在2、3或4位置，包括所有可能的手性碳的构型；B表示i)或ii)式的基团，其中R10表示氢原子，羟基或甲基基团；而R8和R9分别表示，其中R11表示氢或卤素原子，或直链或支链较低烷基基团，Q表示单键，— —，— — —，—O—，—O— —，—S—，—S— —或—CH═CH—，当i)或ii)含有手性中心时，它们可以代表任何构型；X表示单价或多价酸的药学上可接受的阴离子，该阴离子对Hm3亲和力高的胆碱能M3受体具有高亲和力。
• Novel quinuclidine derivatives and medicinal compositions containing the same
  申请人：Fernandez Forner Dolors Maria

  公开号：US20060106055A1

  公开（公告）日：2006-05-18

  A compound according to formula (I) wherein: circle around (C)} is a phenyl ring, a C 4 to C 9 heteroaromatic compound containing one or more heteroatoms, or a naphthalenyl, 5,6,7,8-tetrahydronaphthalenyl or biphenyl group; R 1 , R 2 and R 3 each independently represent a hydrogen or halogen atom, or a hydroxy group, or a phenyl, —OR 4 , —SR 4 , —NR 4 R 5 , —NHCOR 4 , —CONR 4 R 5 , —CN, —NO 2 , —COOR 4 or —CF 3 group, or a straight or branched lower alkyl group which may optionally be substituted, for example, with a hydroxy or alcoxy group, wherein R 4 and R 5 each independently represent a hydrogen atom, straight or branched lower alkyl group, or together form an alicyclic ring; or R 1 and R 2 together form an aromatic, alicyclic or heterocyclic ring; n is an integer from 0 to 4; A represents a —CH 2 —, —CH═CR 6 , —CR 6 ═CH—, —CR 6 R 7 —, —CO—, —O—, —S—, —S(O)—, SO 2 or —NR 6 — group, wherein R 6 and R 7 each independently represent a hydrogen atom, straight or branched lower alkyl group, or R 6 and R 7 together form an alicyclic ring; m is an integer from 0 to 8; provided that when m=0, A is not —CH 2 —; p is an integer from 1 to 2 and the substitution in the azoniabicyclic ring may be in the 2, 3 or 4 position including all possible configurations of the asymmetric carbons; B represents a group of formula i) or ii): wherein R 10 represents a hydrogen atom, a hydroxy or methyl group; and R 8 and R 9 each independently represents wherein R 11 represents a hydrogen or halogen atom, or a straight or branched lower alkyl group and Q represents a single bond, —CH 2 —, —CH 2 —CH 2 —, —O—, —O—CH 2 —, —S—, —S—CH 2 — or —CH═CH—, and when i) or ii) contain a chiral centre they may represent either configuration; X represents a pharmaceutically acceptable anion of a mono or polyvalent acid, which shows high affinity for muscarinic M 3 receptors (Hm3).

  一种化合物，其化学式为（I），其中： 圆圈围绕（C）}为苯环，含有一个或多个杂原子的C4至C9杂环芳香化合物，或萘基，5,6,7,8-四氢萘基或联苯基；R1、R2和R3各自独立地表示氢或卤素原子，或羟基，或苯基，-OR4，-SR4，-NR4R5，-NHCOR4，-CONR4R5，-CN，-NO2，-COOR4或-CF3基团，或可选地被取代的直链或支链低碳烷基，例如，含有羟基或烷氧基的基团，其中R4和R5各自独立地表示氢原子，直链或支链低碳烷基，或一起形成脂环；或R1和R2一起形成芳香，脂环或杂环；n为0至4的整数；A表示-CH2-，-CH═CR6，-CR6═CH-，-CR6R7-，-CO-，-O-，-S-，-S（O）-，SO2或-NR6-基团，其中R6和R7各自独立地表示氢原子，直链或支链低碳烷基，或R6和R7一起形成脂环；m为0至8的整数；但当m=0时，A不为- -；p为1至2的整数，且在氮杂双环环中的取代基可以在2、3或4位，包括不对称碳的所有可能构型；B表示式i）或ii）的基团：其中R10表示氢原子，羟基或甲基基团；而R8和R9各自独立地表示其中R11表示氢或卤素原子，或直链或支链低碳烷基，而Q表示单键，- -，- - -，-O-，-O- -，-S-，-S- -或-CH═CH-，当i）或ii）含有手性中心时，它们可以表示任何构型；X表示单价或多价酸的药学可接受的阴离子，其对肌动蛋白M3受体（Hm3）具有高亲和力。
• Quinuclidine derivatives and medicinal compositions containing the same
  申请人：ALMIRALL, S.A.

  公开号：US10034867B2

  公开（公告）日：2018-07-31

  Provided is a powder inhaler comprising a powder inhalant comprising 3(R)-(2-hydroxy-2,2-dithien-2-ylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane wherein an anion X− is associated with the positive charge of the nitrogen atom and wherein X− is a pharmaceutically acceptable anion of a mono- or polyvalent acid.

  本发明提供了一种粉末吸入剂，该粉末吸入剂包含 3(R)-(2-羟基-2,2-二噻吩-2-基乙酰氧基)-1-(3-苯氧基丙基)-1-氮杂双环[2.2.2]辛烷，其中阴离子 X- 与氮原子的正电荷相关联，且 X- 是单价或多价酸的药学上可接受的阴离子。
• QUINUCLIDINE DERIVATIVES AND THEIR USE AS MUSCARINIC M3 RECEPTORS LIGANDS
  申请人：Almirall, S.A.

  公开号：EP1200431B3

  公开（公告）日：2015-06-24