methyl 4-<<5-(benzyloxycarbonyl)indol-3-yl>methyl>-3-methoxybenzoate | 136564-71-1

• 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: methyl 4-<<5-(benzyloxycarbonyl)indol-3-yl>methyl>-3-methoxybenzoate
• 英文别名: 4-[5-benzoxycarbonyl-1H-indol-3-ylmethyl]-3-methoxy-benzoic acid methylester；methyl 4-(5-benzyloxycarbonylindol-3-ylmethyl)-3-methoxybenzoate；benzyl 3-[(2-methoxy-4-methoxycarbonylphenyl)methyl]-1H-indole-5-carboxylate
• CAS: 136564-71-1
• 化学式: C₂₆H₂₃NO₅
• 分子量: 429.472
• InChiKey: HEVCSPQVZBUOLD-UHFFFAOYSA-N

物化性质

• 沸点：
  623.0±55.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  77.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-<<5-(benzyloxycarbonyl)indol-3-yl>methyl>-3-methoxybenzoate 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.5h， 生成 methyl 4-<<5-carboxy-1-methylindol-3-yl>methyl>-3-methoxybenzoate
  参考文献：
  名称：

  Substituted 3-(phenylmethyl)-1H-indole-5-carboxamides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes

  摘要：

  Substituted indole-5-carboxamides and indole-6-carboxamides have been found to be potent and selective antagonists of the peptidoleukotrienes. Initial derivatives of these series (4-[[5-[(cyclopentylmethyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl] benzamide (5a) and 4-[[6-[(cyclopentylmethyl)carbamoyl]-3-methylindol-1-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (6a), respectively), when compared to the corresponding indole amides (e.g. 28 and 29), were found to be approximately 10-fold less potent in vitro and substantially less active when administered orally to guinea pigs. Efforts to improve the potency of the title series by variation of the amide, indole, or sulfonamide substituents led to compounds of comparable in vitro potency to ICI 204,219, but of somewhat lower oral activity. A trend which suggested that more lipophilic transposed amides were needed to increase oral activity was exploited with some success and has led to the discovery of 5q (4-[[5-[(2-ethylbutyl)-carbamoyl]-1-ethylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide), a trans-posed amide with subnanomolar affinity for the leukotriene receptor and an oral ED50 of 5 mg/kg in a model of asthma in guinea pigs. In this model, ICI 204,219 was active at 0.4 mg/kg. The absolute bioavailability of 5q has been found to be 28% in the rat, as compared to 68% for ICI 204,219, with significant levels of 5q observed in the blood of rats up to 24 h postdose.

  DOI：

  10.1021/jm00055a011
• 作为产物：
  描述：

  吲哚-5-羧酸 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 methyl 4-<<5-(benzyloxycarbonyl)indol-3-yl>methyl>-3-methoxybenzoate
  参考文献：
  名称：

  Substituted 3-(phenylmethyl)-1H-indole-5-carboxamides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes

  摘要：

  Substituted indole-5-carboxamides and indole-6-carboxamides have been found to be potent and selective antagonists of the peptidoleukotrienes. Initial derivatives of these series (4-[[5-[(cyclopentylmethyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl] benzamide (5a) and 4-[[6-[(cyclopentylmethyl)carbamoyl]-3-methylindol-1-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (6a), respectively), when compared to the corresponding indole amides (e.g. 28 and 29), were found to be approximately 10-fold less potent in vitro and substantially less active when administered orally to guinea pigs. Efforts to improve the potency of the title series by variation of the amide, indole, or sulfonamide substituents led to compounds of comparable in vitro potency to ICI 204,219, but of somewhat lower oral activity. A trend which suggested that more lipophilic transposed amides were needed to increase oral activity was exploited with some success and has led to the discovery of 5q (4-[[5-[(2-ethylbutyl)-carbamoyl]-1-ethylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide), a trans-posed amide with subnanomolar affinity for the leukotriene receptor and an oral ED50 of 5 mg/kg in a model of asthma in guinea pigs. In this model, ICI 204,219 was active at 0.4 mg/kg. The absolute bioavailability of 5q has been found to be 28% in the rat, as compared to 68% for ICI 204,219, with significant levels of 5q observed in the blood of rats up to 24 h postdose.

  DOI：

  10.1021/jm00055a011

文献信息

• Indole carbamates as leukotriene antagonists
  申请人：Pfizer Inc

  公开号：US05965745A1

  公开（公告）日：1999-10-12

  Compounds of the formula ##STR1## wherein R.sup.1 AND R.sup.2 are as defined, useful in the treatment of asthma, rheumatoid arthritis, osteoarthritis, bronchitis, chronic obstructive airways diseases, psoriasis, allergic rhinitis, atopic dermatitis, shock, and other inflammatory diseases and for blocking the leucotriene D4 receptor, pharmaceutical compositions containing such compounds and methods of blocking leucotriene D4 receptors using such compositions.

  式##STR1##中R.sup.1和R.sup.2如定义，用于治疗哮喘、类风湿关节炎、骨关节炎、支气管炎、慢性阻塞性气道疾病、牛皮癣、过敏性鼻炎、特应性皮炎、休克和其他炎症性疾病，并用于阻断白三烯D4受体，含有这类化合物的药物组合物以及使用这类组合物阻断白三烯D4受体的方法。
• Carbamoyl derivatives
  申请人：Imperial Chemical Industries PLC

  公开号：US05286740A1

  公开（公告）日：1994-02-15

  The present invention concerns novel carbamoyl derivatives of formula I, set out herein, which antagonize the pharmacological actions of one or more of the arachidonic acid metabolites known as leukotrienes, making them useful whenever such antagonism is desired, such as in the treatment of those diseases in which leukotrienes are implicated, for example, in the treatment of allergic or inflammatory diseases, or of endotoxic or traumatic shock conditions. The invention also provides pharmaceutical compositions containing the novel derivatives for use in such treatments, methods for their use and processes and intermediates for the manufacture of the novel derivatives.

  本发明涉及一种新的氨基甲酰衍生物，其化学式为I，该衍生物在此处列出，能拮抗被称为白三烯的花生四烯酸代谢产物的药理作用，使其在需要拮抗这种作用的情况下非常有用，例如在白三烯参与的疾病治疗中，例如在过敏性或炎症性疾病的治疗中，或在内毒素性或创伤性休克症状的治疗中。该发明还提供了含有这些新衍生物的药物组合物，用于进行这种治疗的方法，以及用于制造这些新衍生物的方法和中间体。
• A process for the preparation of a 3-alkylated indole, intermediates, and a process for the preparation of a derivative thereof
  申请人：ZENECA LIMITED

  公开号：EP0489547B1

  公开（公告）日：1998-07-29
• Jacobs Robert T., Brown Frederick J., Cronk Laura A., Aharony David, Buck+, J. Med. Chem., 36 (1993) N 3, S 394-409
  作者：Jacobs Robert T., Brown Frederick J., Cronk Laura A., Aharony David, Buck+

  DOI：——

  日期：——
• US5280125A
  申请人：——

  公开号：US5280125A

  公开（公告）日：1994-01-18