3-Isopropenyl-2(3H)-naphtho[2,3-d]imidazolone | 178042-28-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-Isopropenyl-2(3H)-naphtho[2,3-d]imidazolone
• 英文别名: 3-prop-1-en-2-yl-1H-benzo[f]benzimidazol-2-one
• CAS: 178042-28-9
• 化学式: C₁₄H₁₂N₂O
• 分子量: 224.262
• InChiKey: WRDXGMULMHOJDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-Isopropenyl-2(3H)-naphtho[2,3-d]imidazolone 、 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-{2-[4-(N-Propionylanilino)piperidino]ethyl}-3-isopropenyl-2(3H)-naphtho[2,3-d]imidazolone
  参考文献：
  名称：

  Pharmacological profile of a novel series of NK1 antagonists. In vitro and in vivo potency of benzimidazolone derivatives

  摘要：

  By low throughput examination of our chemical library, compound 7 was selected as a lead NK, antagonist with a K-i of 7.1 nM. Modifications of its structure led to the finding that the in vitro potency could be markedly enhanced by disubstituting the anilino phenyl ring as in compounds 13 or 22. Human binding data correlated rather well with results obtained with in vitro animal mice; compound 13 was the most active with ED50 of 0.001 and 0.3 mg/kg after iv and po administration respectively. Furthermore, antagonist 71 was found to be a potent inhibitor of SP-induced bronchoconstriction in guinea-pigs with an ED50 between 0.1 and 0.03 mg/kg iv. Furthermore, upon oral administration, 71 was observed to be active in a model of SP-induced bronchial hypersensitivity in mice, with an ID50 of around 3 mg/kg.

  DOI：

  10.1016/s0223-5234(97)82771-7
• 作为产物：
  描述：

  2,3-二氨基萘 、 乙酰乙酸甲酯 在 氢氧化钾 作用下， 以 水 、 xylene 为溶剂， 生成 3-Isopropenyl-2(3H)-naphtho[2,3-d]imidazolone
  参考文献：
  名称：

  Pharmacological profile of a novel series of NK1 antagonists. In vitro and in vivo potency of benzimidazolone derivatives

  摘要：

  By low throughput examination of our chemical library, compound 7 was selected as a lead NK, antagonist with a K-i of 7.1 nM. Modifications of its structure led to the finding that the in vitro potency could be markedly enhanced by disubstituting the anilino phenyl ring as in compounds 13 or 22. Human binding data correlated rather well with results obtained with in vitro animal mice; compound 13 was the most active with ED50 of 0.001 and 0.3 mg/kg after iv and po administration respectively. Furthermore, antagonist 71 was found to be a potent inhibitor of SP-induced bronchoconstriction in guinea-pigs with an ED50 between 0.1 and 0.03 mg/kg iv. Furthermore, upon oral administration, 71 was observed to be active in a model of SP-induced bronchial hypersensitivity in mice, with an ID50 of around 3 mg/kg.

  DOI：

  10.1016/s0223-5234(97)82771-7

文献信息

• Piperidine compounds
  申请人：Adir et Compagnie

  公开号：US05652246A1

  公开（公告）日：1997-07-29

  The invention relates to the compounds of formula (I): ##STR1## in which: R.sub.1 represents alkyl, phenyl, naphthyl, pyridyl or thienyl group, each phenyl, naphthyl, pyridyl or thienyl optionally being substituted, R.sub.2 represents a hydrogen atom or a substituted or unsubstituted alkyl, substituted or unsubstituted phenyl, cycloalkyl, piperidino or substituted or unsubstituted amino group, X represents CO or SO.sub.2, R.sub.3 represents hydrogen or alkyl, R.sub.4 represents alkyl, substituted or unsubstituted phenyl or trihalomethyl, or else R.sub.3 and R.sub.4 form, together with the carbon atoms which carry them, cyclo(C.sub.3 -C.sub.7)alkenyl, A represents phenyl, naphthyl or pyridyl ring, each phenyl, naphthyl or pyridyl ring optionally being substituted, their isomers, the corresponding quaternary ammonium salts of the piperidine and their addition salts with a pharmaceutically acceptable acid, an medicinal products containing the same are useful as antagonists of NK.sub.1 receptors.

  该发明涉及以下公式（I）的化合物：##STR1## 在其中：R.sub.1代表烷基，苯基，萘基，吡啶基或噻吩基，每个苯基，萘基，吡啶基或噻吩基可选择地被取代，R.sub.2代表氢原子或取代或未取代的烷基，取代或未取代的苯基，环烷基，哌啶基或取代或未取代的氨基，X代表CO或SO.sub.2，R.sub.3代表氢或烷基，R.sub.4代表烷基，取代或未取代的苯基或三卤甲基，否则R.sub.3和R.sub.4与携带它们的碳原子一起形成环（C.sub.3 -C.sub.7）烯基，A代表苯基，萘基或吡啶环，每个苯基，萘基或吡啶环可选择地被取代，它们的异构体，哌啶的相应季铵盐及其与药学上可接受的酸形成的加合盐，含有它们的药物制剂作为NK.sub.1受体的拮抗剂是有用的。
• Nouveaux dérivés de pipéridine utiles comme antagonistes des récepteurs des neurokinines
  申请人：ADIR ET COMPAGNIE

  公开号：EP0708101A1

  公开（公告）日：1996-04-24

  Composés de formule (I) : dans laquelle : R₁ représente un groupement alkyle, phényle, naphtyle, pyridyle ou thiényle, chaque groupement phényle, naphtyle, pyridyle ou thiényle étant éventuellement substitué, R₂ représente un atome d'hydrogène, un groupement alkyle substitué ou non, phényle substitué ou non, cycloalkyle, pipéridino ou amino substitué ou non, X représente un groupement CO ou SO₂, R₃ représente un atome d'hydrogène ou un groupement alkyle, R₄ représente un groupement alkyle, un groupement phényle substitué ou non ou un groupement trihalogénométhyle, ou bien, R₃ et R₄ forment ensemble avec les atomes de carbone qui les portent un groupement cycloalkényl(C₃-C₇), A représente un cycle phényle, naphtyle, pyridyle, chaque cycle phényle, naphtyle, pyridyle étant éventuellement substitué, leurs isomères, les sels d'ammonium quaternaire de la pipéridine correspondants ainsi que leurs sels d'addition à un acide pharmaceutiquement acceptable. Médicaments.

  式(I)化合物： 其中 R₁ 代表烷基、苯基、萘基、吡啶基或噻吩基，每个苯基、萘基、吡啶基或噻吩基均任选被取代、 R₂ 代表氢原子、取代或未取代的烷基、取代或未取代的苯基、环烷基、哌啶基或取代或未取代的氨基、 X 代表 CO 或 SO₂ 基团、 R₃ 代表氢原子或烷基、 R₄ 代表烷基、取代或未取代的苯基或三卤甲基、 或 R₃ 和 R₄ 与携带它们的碳原子一起形成环烯基 (C₃-C₇)、 A 代表苯基、萘基或吡啶基环，每个苯基、萘基或吡啶基环均被任选取代、 它们的异构体、相应的哌啶季铵盐及其与药学上可接受的酸的加成盐。 药用产品。
• Dérivés de pipéridine utiles comme antagonistes des récepteurs des neurokinines
  申请人：ADIR ET COMPAGNIE

  公开号：EP0708101B1

  公开（公告）日：1998-12-09
• US5652246A
  申请人：——

  公开号：US5652246A

  公开（公告）日：1997-07-29
• Pharmacological profile of a novel series of NK1 antagonists. In vitro and in vivo potency of benzimidazolone derivatives
  作者：G Rémond、B Portevin、J Bonnet、E Canet、D Regoli、G De Nanteuil

  DOI：10.1016/s0223-5234(97)82771-7

  日期：1997.11

  By low throughput examination of our chemical library, compound 7 was selected as a lead NK, antagonist with a K-i of 7.1 nM. Modifications of its structure led to the finding that the in vitro potency could be markedly enhanced by disubstituting the anilino phenyl ring as in compounds 13 or 22. Human binding data correlated rather well with results obtained with in vitro animal mice; compound 13 was the most active with ED50 of 0.001 and 0.3 mg/kg after iv and po administration respectively. Furthermore, antagonist 71 was found to be a potent inhibitor of SP-induced bronchoconstriction in guinea-pigs with an ED50 between 0.1 and 0.03 mg/kg iv. Furthermore, upon oral administration, 71 was observed to be active in a model of SP-induced bronchial hypersensitivity in mice, with an ID50 of around 3 mg/kg.