3-[4-(3,6-二氢-4-苯基-1(2H)-吡啶基)丁基]-1H-吲哚-5-醇盐酸盐 | 108050-82-4

• 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
• 中文名称: 3-[4-(3,6-二氢-4-苯基-1(2H)-吡啶基)丁基]-1H-吲哚-5-醇盐酸盐
• 英文名称: Roxindole hydrochloride
• 英文别名: 3-[4-(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)butyl]-1H-indol-1-ium-5-ol;chloride
• CAS: 108050-82-4
• 化学式: C₂₃H₂₆N₂O*ClH
• 分子量: 382.933
• InChiKey: ZCEPVNSWLLJECX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.41
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  39.3
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-[4-(3,6-二氢-4-苯基-1(2H)-吡啶基)丁基]-1H-吲哚-5-醇盐酸盐 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以63%的产率得到3-[4-(4-Phenyl-piperidin-1-yl)-butyl]-1H-indol-5-ol
  参考文献：
  名称：

  Indolebutylamines as Selective 5-HT_1A Agonists

  摘要：

  A series of new 1-[4-(indol-3-yl)butyl]-4-arylpiperazines was prepared to identify highly selective and potent 5-HT1A agonists as potential pharmacological tools in studies of mood disorders. The combination of structural elements (indole-alkyl-amine and aryl-piperazine) known to introduce 5-HT1A receptor affinity and the proper selection of substituents (R on the indole moiety and R' on the aryl moiety) led to compounds with high receptor specificity and affinity. In particular, the introduction of the methyl ether or the unsubstituted carboxamide as substituents in position 5 of the indole (R) guaranteed serotonergic 5-HT1A affinity compared to the unsubstituted analogue. Para-substituted arylpiperazines (R') decreased dopaminergic D-2 binding and increased selectivity for the 5-HT1A receptor. Agonistic 5-HT1A receptor activity was confirmed in vivo in the ultrasonic vocalization test, and the results suggest that the introduction of the carboxamide residue leads to better bioavailability than the corresponding methyl ether. 3-{4-[4-(4-Carbamoylphenyl)piperazin-1-yl}butyl}-1H-indole-5-carboxamide 54 was identified as a highly selective 5-HT1A receptor agonist [GTPgammaS, ED50 = 4.7 nM] with nanomolar 5-HT1A affinity [IC50 = 0.9 nM] and selectivity [D-2, IC50 > 850 nM]. 3-{4-[4-(4-Methoxyphenyl)piperazin-1-yl]butyl}-1H-indole-5-carboxamide 45 is one of the most potent and selective 5-HT1A agonists known [5-HT1A, IC50 = 0.09 nM; D-2, IC50 = 140 nM].

  DOI：

  10.1021/jm040792y

文献信息

• Combination therapies
  申请人：Pfizer Inc

  公开号：US20040209916A1

  公开（公告）日：2004-10-21

  The invention is directed to methods of treating asthma, COPD, allergic rhinitis, and infectious rhinitis by administering a first pharmaceutical agent including one or more compounds selected from the quarternary ammonium compounds of formulae I-V and a second pharmaceutical agent including one or more pharmaceutical agents selected from Adenosine A 2a Receptor Agonists, D2-Dopamine Receptor Agonists, Phosphodiesterase Inhibitors (PDE's), corticosteroids, norepinephrine reuptake inhibitors, 4-hydroxy-7-[2-[2-[3-[2-phenylethoxy]-propylsulphonyl]ethylamino]ethyl]-1,3-benzothiazol-2(3H)-one, and pharmaceutically acceptable salts thereof, and non-quarternized antimuscarinic compounds.

  该发明涉及通过给予包括公式I-V的季铵化合物中选取的一个或多个化合物以及包括选自腺苷A2a受体激动剂、D2-多巴胺受体激动剂、磷酸二酯酶抑制剂（PDE's）、皮质类固醇、去甲肾上腺素再摄取抑制剂、4-羟基-7-[2-[2-[3-[2-苯乙氧基]-丙磺酰乙氨基]-乙基]-1,3-苯并噻唑-2(3H)-酮及其药用可接受的盐以及非季铵化的抗胆碱药物的第二药物，来治疗哮喘、COPD、过敏性鼻炎和感染性鼻炎的方法。
• COMBINATION OF A DOPAMINE D2-RECEPTOR AGONIST AND TIOTROPIUM OR A DERIVATIVE THEROF FOR TREATING OBSTRUCTIVE AIRWAYS
  申请人：Boehringer Ingelheim Pharma GmbH & Co.KG

  公开号：EP1397134A2

  公开（公告）日：2004-03-17
• Combination of a dopamine D2-receptor agonist and tiotropium or a derivative therof for treating obstructive airways and other inflammatory diseases
  申请人：Yeadon Michael

  公开号：US20070117788A1

  公开（公告）日：2007-05-24

  The present invention relates to a combination of therapeutic agents useful in the treatment of obstructive airways and other inflammatory diseases comprising (I) a dopamine D2-receptor agonist that is therapeutically effective in the treatment of said diseases when administered by inhalation; together with (II) an anti-cholinergic agent consisting of a member selected from the group consisting of tiotropium and derivatives thereof that is therapeutically effective in the treatment of said diseases when administered by inhalation; as well as to a method of treating said obstructive airways and other inflammatory diseases comprising administering to said mammal by inhalation a therapeutically effective amount of said combination of therapeutic agents; and a pharmaceutical composition comprising a pharmaceutically acceptable carrier together with said combination of therapeutic agents; and a package containing a pharmaceutical composition for insertion into a device capable of simultaneous or sequential delivery of said pharmaceutical composition in the form of an aerosol or dry powder dispersion to said mammal, where said device is a metered dose inhaler or a dry powder inhaler. It is preferred that said dopamine D2-receptor agonist component be bromocriptine mesylate, naxagolide hydrochloride, cabergoline, pergolide mesylate, quinpirole hydrochloride, or ropinirole hydrochloride; and that said anti-cholinergic agent component be tiotropium bromide.
• [EN] COMBINATION OF A DOPAMINE D2-RECEPTOR AGONIST AND TIOTROPIUM OR A DERIVATIVE THEREOF FOR TREATING OBSTRUCTIVE AIRWAYS AND OTHER INFLAMMATORY DISEASES<br/>[FR] COMBINAISON D'UN AGONISTE DE RECEPTEUR DE DOPAMINE D2 ET DE TIOTROPIUM OU D'UN DERIVE DE CELUI-CI, DESTINEE AU TRAITEMENT DES VOIES RESPIRATOIRES OBSTRUCTIVES ET D'AUTRES MALADIES INFLAMMATOIRES
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2002096422A2

  公开（公告）日：2002-12-05

  The present invention relates to a combination of therapeutic agents useful in the treatment of obstructive airways and other inflammatory diseases comprising (I) a dopamine D2-receptor agonist that is therapeutically effective in the treatment of said diseases when administered by inhalation; together with (II) an anti-cholinergic agent consisting of a member selected from the group consisting of tiotropium and derivatives thereof that is therapeutically effective in the treatment of said diseases when administered by inhalation; as well as to a method of treating treating said obstructive airways and other inflammatory diseases comprising administering to said mammal by inhalation a therapeutically effective amount of said combination of therapeutic agents; and a pharmaceutical composition comprising a pharmaceutically acceptable carrier together with said combination of therapeutic agents; and a package containing a pharmaceutical composition for insertion into a device capable of simultaneous or sequential delivery of said pharmaceutical composition in the form of an aerosol or dry powder dispersion to said mammal, where said device is a metered dose inhaler or a dry powder inhaler. It is preferred that said dopamine D2-receptor agonist component be bromocriptine mesylate, naxagolide hydrochloride, cabergoline, pergolide mesylate, quinpirole hydrochloride, or ropinirole hydrochloride; and that said anti-cholinergic agent component be tiotropium bromide.