6-<(cyclopentylmethyl)carbamoyl>indole | 104447-78-1

• 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: 6-<(cyclopentylmethyl)carbamoyl>indole
• 英文别名: 6-indole；6-(N-cyclopentylmethylcarbamoyl)indole；N-(cyclopentylmethyl)-1H-indole-6-carboxamide
• CAS: 104447-78-1
• 化学式: C₁₅H₁₈N₂O
• mdl: MFCD19107175
• 分子量: 242.321
• InChiKey: SXICMFHLMXZHDO-UHFFFAOYSA-N

物化性质

• 沸点：
  511.5±23.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  44.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-<(cyclopentylmethyl)carbamoyl>indole 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以60%的产率得到6-<(cyclopentylmethyl)carbamoyl>-3-formylindole
  参考文献：
  名称：

  Heterocyclic carboxamides

  摘要：

  这项发明提供了一系列新颖的杂环羧酰胺，其化学式为I，其中基团--Y--Z<选择自--C(Ra).dbd.C<，--N.dbd.C<和--CH(Ra)--CH<，其他基团的含义在以下说明中定义。化学式I的化合物是白三烯拮抗剂。该发明还提供了化学式I化合物的药学上可接受的盐；含有化学式I化合物或其盐的药物组合物，用于治疗过敏性或炎症性疾病，或内毒素性或创伤性休克等疾病；以及用于制造化学式I化合物的工艺，以及用于该制造的中间体。

  公开号：

  US04898863A1
• 作为产物：
  描述：

  (E)-1-(dimethylamino)-2-[4-(methoxycarbonyl)-2-nitrophenyl]ethene 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 60.0 ℃ 、344.73 kPa 条件下， 反应 7.58h， 生成 6-<(cyclopentylmethyl)carbamoyl>indole
  参考文献：
  名称：

  1,3,6-三取代的吲哚作为肽白三烯拮抗剂：具有第二个极性吡咯取代基的优点。

  摘要：

  含有酰基氨基和N-芳基磺酰基酰胺附件的1，6-取代的和3,5-取代的吲哚和吲唑是肽白三烯LTD4和LTE4的有效拮抗剂。3，5-取代的吲哚系列的化合物，N- [4-[[5-[[（环戊氧基）]]]甲基] [甲基] [3-基]甲基] -3-甲氧基苯甲酰基] -2-甲基-苯磺酰胺（ICI 204,219）正在接受哮喘的临床评估。该系列拮抗剂引入了结构多样性的两个新元素。对1，6-取代的吲哚中吡咯取代基的研究表明，C-2处的取代对生物活性有害，但在C-3处引入亲水基团是有益的。在C-3处引入丙酰胺部分将活性提高了1个数量级。N- [4-[[6-（环戊基乙酰胺基）-3-] [2-（N-甲基氨基甲酰基）乙基]吲哚-1-基]甲基] -3-甲氧基-苯甲酰基]苯磺酰胺（15c）的pKB为10.7豚鼠气管上的LTD4受体。二取代拮抗剂的酰基氨基部分的修饰表明酰胺CO和NH原子的转位是可行的。在1，6-和3，5

  DOI：

  10.1021/jm00091a010

文献信息

• Indazole compounds, pharmaceutical compositions and use
  申请人：ICI Americas Inc.

  公开号：US04997844A1

  公开（公告）日：1991-03-05

  The invention provides a series of novel heterocyclic amides of the formula I in which the group A CRa can be --CRb.dbd.CRa--, --CHRb--CHRa-- or --N.dbd.CRa--, the amidic group Re.L can be Re.X.CO.NH, Re.X.CS.NH or Re.NH.CO attached at position 4, 5 or 6 of the benzenoid moiety, Z is an acid group selected from the group consisting of carboxy, an acylsulphonamide residue of the formula CO.NH.SO.sub.n Rg and a tetrazolyl residue of the formula II, and the radicals Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, n, X, G.sup.1, Q and G.sup.2 have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compounds, or their salts, for use in the treatment of, for example, allergic or inflammatory diseases, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.

  该发明提供了一系列新颖的杂环酰胺，其化学式为I，在该化学式中，基团A CRa可以是--CRb.dbd.CRa--，--CHRb--CHRa--或--N.dbd.CRa--，酰胺基团Re.L可以是连接在苯环部分的第4、5或6位的Re.X.CO.NH，Re.X.CS.NH或Re.NH.CO，Z是从羧基、公式CO.NH.SO.sub.n Rg的酰磺胺残基或公式II的四唑基残基中选择的酸基团，基团Ra、Rb、Rc、Rd、Re、Rf、Rg、Rh、n、X、G.sup.1、Q和G.sup.2的含义在以下说明中定义。化合物I的化学式是白三烯拮抗剂。该发明还提供了化合物I的药学上可接受的盐；含有化合物I或其盐的药物组合物，用于治疗过敏性或炎症性疾病、内毒素性休克或创伤性休克等疾病；以及用于制造化合物I的方法，以及用于该制造的中间体。
• Substituted 3-(phenylmethyl)-1H-indole-5-carboxamides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes
  作者：Robert T. Jacobs、Frederick J. Brown、Laura A. Cronk、David Aharony、Carl K. Buckner、Edward J. Kusner、Karin M. Kirkland、Kathleen L. Neilson

  DOI：10.1021/jm00055a011

  日期：1993.2

  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.
• 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：——
• US4898863A
  申请人：——

  公开号：US4898863A

  公开（公告）日：1990-02-06
• Heterocyclic carboxamides
  申请人：ICI Americas Inc.

  公开号：US04898863A1

  公开（公告）日：1990-02-06

  This invention provides a series of novel heterocyclic carboxamides of formula I in which the group --Y--Z< is selected from --C(Ra).dbd.C<, --N.dbd.C<, and --CH(Ra)--CH< and the other radicals have the meanings defined in the following specification. The compounds of formula I are leukotriene antagonists. The invention also provides pharmaceutically acceptable salts of the formula I compounds; pharmaceutical compositions containing the formula I compound, or their salts, for use in the treatment of, for example, allergic or inflammatory diseasxes, or endotoxic or traumatic shock conditions; and processes for the manufacture of the formula I compounds, as well as intermediates for use in such manufacture.

  这项发明提供了一系列新颖的杂环羧酰胺，其化学式为I，其中基团--Y--Z<选择自--C(Ra).dbd.C<，--N.dbd.C<和--CH(Ra)--CH<，其他基团的含义在以下说明中定义。化学式I的化合物是白三烯拮抗剂。该发明还提供了化学式I化合物的药学上可接受的盐；含有化学式I化合物或其盐的药物组合物，用于治疗过敏性或炎症性疾病，或内毒素性或创伤性休克等疾病；以及用于制造化学式I化合物的工艺，以及用于该制造的中间体。