4-phenyl-1-(3(R)-[3,4-dichlorophenyl]-4-[2-(1,2,3,4-tetrahydro-5-naphthoyl)imidazol-1-yl]butyl)quinuclidinium methanesulphonate | 217431-88-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-phenyl-1-(3(R)-[3,4-dichlorophenyl]-4-[2-(1,2,3,4-tetrahydro-5-naphthoyl)imidazol-1-yl]butyl)quinuclidinium methanesulphonate
• 英文别名: [1-[(2R)-2-(3,4-dichlorophenyl)-4-(4-phenyl-1-azoniabicyclo[2.2.2]octan-1-yl)butyl]imidazol-2-yl]-(5,6,7,8-tetrahydronaphthalen-1-yl)methanone;methanesulfonate
• CAS: 217431-88-4
• 化学式: CH₃O₃S*C₃₇H₄₀Cl₂N₃O
• 分子量: 708.749
• InChiKey: WAAMLEYKDDMXCE-BSFXUQRGSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  7.59
• 重原子数：
  48
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-苯基奎宁环 、 1-methanesulphonyloxy-3(R)-(3,4-dichlorophenyl)-4-[2-(1,2,3,4-tetrahydro-5-naphthoyl)imidazol-1-yl]butane 生成 4-phenyl-1-(3(R)-[3,4-dichlorophenyl]-4-[2-(1,2,3,4-tetrahydro-5-naphthoyl)imidazol-1-yl]butyl)quinuclidinium methanesulphonate
  参考文献：
  名称：

  Quaternary ammonium compounds as tachykinin antagonists

  摘要：

  本发明提供了一种具有化学式(I)的化合物，其中R为苯基、C3-C7环烷基或杂环芳基，每种基团均可选择性地与苯基或C3-C7环烷基融合，并可选择性地被从1到3个取代基取代，每个取代基独立地选自C1-C4烷基、氟代(C1-C4)烷基、C1-C4烷氧基、氟代(C1-C4)烷氧基、苯氧基、C2-C4烷酰基、卤素、C1-C4烷氧羰基、C3-C7环烷基、—S(O)m(C1-C4烷基)、氰基、—NR2R3、—S(O)mNR2R3、—NR4(C1-C4烷酰基)和—CONR2R3，或者R为2,3-二氢苯并[b]呋喃基或色基；R1为H或C1-C6烷基；W为直链、亚甲基或乙烯基；X为直链C2-C4烷基；Y为苯基、萘基、苄基、吡啶基、噻吩基或C3-C7环烷基，每个基团均可选择性地被从1到3个取代基取代，每个取代基独立地选自C1-C4烷基、氟代(C1-C4)烷基、C1-C4烷氧基、氟代(C1-C4)烷氧基、卤素和氰基；Ar为苯基、萘基、苄基、噻吩基、苯并[b]噻吩基或吲哚基，每个基团均可选择性地被从1到3个取代基取代，每个取代基独立地选自C1-C4烷基、氟代(C1-C4)烷基、C1-C4烷氧基、氟代(C1-C4)烷氧基、卤素和氰基，或者Ar为1,3-苯并二氧杜嗪-4或5-基或1,4-苯并二氧杜嗪-5或6-基；ZA为药用可接受的阴离子；但要求当W为直链且R为可选择地融合和可选择地取代的杂环芳基时，所述杂环芳基通过一个环碳原子与酰基团相连。这些化合物是Tachykinin拮抗剂。

  公开号：

  US06207678B1

文献信息

• QUATERNARY AMMONIUM COMPOUNDS AS TACHYKININ ANTAGONISTS
  申请人：Pfizer Limited

  公开号：EP0994876A1

  公开（公告）日：2000-04-26
• US6207678B1
  申请人：——

  公开号：US6207678B1

  公开（公告）日：2001-03-27
• US6380396B1
  申请人：——

  公开号：US6380396B1

  公开（公告）日：2002-04-30
• [EN] QUATERNARY AMMONIUM COMPOUNDS AS TACHYKININ ANTAGONISTS<br/>[FR] COMPOSES D'AMMONIUM QUATERNAIRE UTILES EN TANT QU'ANTAGONISTES DES TACHYKININES
  申请人：PFIZER LIMITED

  公开号：WO1998057972A1

  公开（公告）日：1998-12-23

  (EN) The present invention provides a compound of formula (I) wherein R is phenyl, C3-C7 cycloalkyl or heteroaryl, each of which being optionally benzo- or C3-C7 cycloalkyl-fused and optionally substituted, including in the benzo- or C3-C7 cycloalkyl-fused portion, by from 1 to 3 substituents each independently selected from C1-C4 alkyl, fluoro(C1-C4)alkyl, C1-C4 alkoxy, fluoro(C1-C4)alkoxy, phenoxy, C2-C4 alkanoyl, halo, C1-C4 alkoxycarbonyl, C3-C7 cycloalkyl, -S(O)m(C1-C4 alkyl), cyano, -NR2R3, -S(O)mNR2R3, -NR4(C1-C4 alkanoyl) and -CONR2R3, or R is 2,3-dihydrobenzo[b]furanyl or chromanyl; R1 is H or C1-C6 alkyl; W is a direct link, methylene or ethylene; X is unbranched C2-C4 alkylene; Y is phenyl, naphthyl, benzyl, pyridyl, thienyl or C3-C7 cycloalkyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4 alkyl, fluoro(C1-C4)alkyl, C1-C4 alkoxy, fluoro(C1-C4)alkoxy, halo and cyano; Ar is phenyl, naphthyl, benzyl, thienyl, benzo[b]thienyl or indolyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4 alkyl, fluoro(C1-C4)alkyl, C1-C4 alkoxy, fluoro(C1-C4)alkoxy, halo and cyano, or Ar is 1,3-benzodioxolan-4 or 5-yl or 1,4-benzodioxan-5 or 6-yl; ZA is a pharmaceutically acceptable anion; with the proviso that when W is a direct link and R is optionally fused and optionally substituted heteroaryl, said heteroaryl is linked by a ring carbon atom to the carbonyl group. The compounds are tachykinin antagonists.(FR) La présente invention concerne un composé de la formule (I) dans laquelle R représente phényle, cycloalkyle C3-C7 ou hétéroaryle, chacun de ceux-ci étant éventuellement benzo- ou cycloalkyle C3-C7-condensé, et éventuellement substitué, notamment dans la portion benzo-condensée ou cycloalkyle C3-C7-condensée, par 1 à 3 substituants choisis chacun indépendamment dans le groupe constitué par alkyle C1-C4, fluoro-alkyle C1-C4, alcoxy C1-C4, fluoro-alcoxy C1-C4, phénoxy, alcanoyle C2-C4, halo, alcoxycarbonyle C1-C4, cycloalkyle C3-C7, -S(O)m(alkyle C1-C4), cyano, -NR2R3, -S(O)mNR2R3, -NR4(alcanoyle C1-C4) et -CONR2R3, ou bien R représente 2,3-dihydrobenzo[b]furanyle ou chromanyle; R1 représente H ou alkyle C1-C6, W représente une liaison directe, méthylène ou éthylène, X représente alkylène C2-C4 non ramifié, Y représente phényle, naphtyle, benzyle, pyridyle, thiényle ou cycloalkyle C3-C7, chacun étant éventuellement substitué par 1 à 3 substituants choisis indépendamment dans le groupe par alkyle C1-C4, fluoro-alkyle C1-C4, alcoxy C1-C4, fluoro-alcoxy C1-C4, halo et cyano; Ar représente phényle, naphtyle, benzyle, thiényle, benzo[b]thiényle ou indolyle, chacun étant éventuellement substitué par 1 à 3 substituants choisis indépendamment dans le groupe constitué par alkyle C1-C4, fluoro-alkyle C1-C4, alcoxy C1-C4, fluoro-alcoxy C1-C4, halo et cyano, ou bien Ar représente 1,3-benzodioxolan-4 ou 5-yle, ou 1,4-benzodioxan-5 ou 6-yle et ZA représente un anion acceptable sur le plan pharmacologique, à la condition que lorsque W représente une liaison directe et que R représente hétéroaryle éventuellement condensé et éventuellement substitué, cet hétéroaryle soit lié par un atome de carbone du noyau au groupe carbonyle. Ces composés constituent des antagonistes des tachykinines.
• Quaternary ammonium compounds as tachykinin antagonists
  申请人：Pfizer INC

  公开号：US06207678B1

  公开（公告）日：2001-03-27

  The present invention provides a compound of formula (I) wherein R is phenyl, C3-C7 cycloalkyl or heteroaryl, each of which being optionally benzo- or C3-C7 cycloalkyl-fused and optionally substituted, including in the benzo- or C3-C7 cycloalkyl-fused portion, by from 1 to 3 substituents each independently selected from C1-C4 alkyl, fluoro(C1-C4)alkyl, C1-C4 alkoxy, fluoro(C1-C4)alkoxy, phenoxy, C2-C4 alkanoyl, halo, C1-C4 alkoxycarbonyl, C3-C7 cycloalkyl, —S(O)m(C1-C4 alkyl), cyano, —NR2R3, —S(O)mNR2R3, —NR4(C1-C4 alkanoyl) and —CONR2R3, or R is 2,3-dihydrobenzo[b]furanyl or chromanyl; R1 is H or C1-C6 alkyl; W is a direct link, methylene or ethylene; X is unbranched C2-C4 alkylene; Y is phenyl, naphthyl, benzyl, pyridyl, thienyl or C3-C7 cycloalkyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4 alkyl, fluoro(C1-C4)alkyl, C1-C4 alkoxy, fluoro(C1-C4)alkoxy, halo and cyano; Ar is phenyl, naphthyl, benzyl, thienyl, benzo[b]thienyl or indolyl, each of which being optionally substituted by from 1 to 3 substituents each independently selected from C1-C4 alkyl, fluoro(C1-C4)alkyl, C1-C4 alkoxy, fluoro(C1-C4)alkoxy, halo and cyano, or Ar is 1,3-benzodioxolan-4 or 5-yl or 1,4-benzodioxan-5 or 6-yl; ZA is a pharmaceutically acceptable anion; with the proviso that when W is a direct link and R is optionally fused and optionally substituted heteroaryl, said heteroaryl is linked by a ring carbon atom to the carbonyl group. The compounds are tachykinin antagonists.

  本发明提供了一种具有化学式(I)的化合物，其中R为苯基、C3-C7环烷基或杂环芳基，每种基团均可选择性地与苯基或C3-C7环烷基融合，并可选择性地被从1到3个取代基取代，每个取代基独立地选自C1-C4烷基、氟代(C1-C4)烷基、C1-C4烷氧基、氟代(C1-C4)烷氧基、苯氧基、C2-C4烷酰基、卤素、C1-C4烷氧羰基、C3-C7环烷基、—S(O)m(C1-C4烷基)、氰基、—NR2R3、—S(O)mNR2R3、—NR4(C1-C4烷酰基)和—CONR2R3，或者R为2,3-二氢苯并[b]呋喃基或色基；R1为H或C1-C6烷基；W为直链、亚甲基或乙烯基；X为直链C2-C4烷基；Y为苯基、萘基、苄基、吡啶基、噻吩基或C3-C7环烷基，每个基团均可选择性地被从1到3个取代基取代，每个取代基独立地选自C1-C4烷基、氟代(C1-C4)烷基、C1-C4烷氧基、氟代(C1-C4)烷氧基、卤素和氰基；Ar为苯基、萘基、苄基、噻吩基、苯并[b]噻吩基或吲哚基，每个基团均可选择性地被从1到3个取代基取代，每个取代基独立地选自C1-C4烷基、氟代(C1-C4)烷基、C1-C4烷氧基、氟代(C1-C4)烷氧基、卤素和氰基，或者Ar为1,3-苯并二氧杜嗪-4或5-基或1,4-苯并二氧杜嗪-5或6-基；ZA为药用可接受的阴离子；但要求当W为直链且R为可选择地融合和可选择地取代的杂环芳基时，所述杂环芳基通过一个环碳原子与酰基团相连。这些化合物是Tachykinin拮抗剂。