3-{[3-(5-fluoro-1H-indol-3-yl)propyl]amino}chromane-5-carboxamide hydrochloride | 843656-57-5

• 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: 3-{[3-(5-fluoro-1H-indol-3-yl)propyl]amino}chromane-5-carboxamide hydrochloride
• 英文别名: 3-{[3-(5-fluoro-1H-indol-3-yl)propyl]amino}chromane-5-carboxamide；3-[3-(5-fluoro-1H-indol-3-yl)propylamino]-3,4-dihydro-2H-chromene-5-carboxamide
• CAS: 843656-57-5
• 化学式: C₂₁H₂₂FN₃O₂
• 分子量: 367.423
• InChiKey: IASYKMFFYXBPNW-UHFFFAOYSA-N

物化性质

• 熔点：
  153-155 °C
• 沸点：
  585.8±50.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  80.1
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{[3-(5-fluoro-1H-indol-3-yl)propyl]amino}chromane-5-carboxamide hydrochloride 、 丙醛 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 3-{[3-(5-fluoro-1H-indol-3-yl)propyl](propyl)amino}chromane-5-carboxamide
  参考文献：
  名称：

  Advances toward New Antidepressants with Dual Serotonin Transporter and 5-HT_1A Receptor Affinity within a Class of 3-Aminochroman Derivatives. Part 2

  摘要：

  Novel compounds combining a 5-HT1A moiety (3-aminochroman scaffold) and a 5-HT transporter (indole analogues) linked through,a common basic nitrogen via an alkyl chain attached at the 1- or 3-position of the indole were evaluated for dual affinity at both the 5-HT reuptake site and the 5-HT1A receptor. Compounds of most interest were found to have a 5-carbamoyl-8-fluoro-3-amino-3,4-dihydro-2H-1-benzopyran linked to a 3-alkylindole (straight chain), more specifically substituted with a 5-fluoro ((R)-(-)-35c), 5-cyano ((-)-52a), or 5,7-difluoro ((-)-52g). Several factors contributed to 5-HT1A affinity, serotonin rat transporter affinity, and functional antagonism in vitro. Although most of our analogues showed good to excellent affinities at both targets, specific features such as cyclobutyl substitution on the basic nitrogen and stereochemistry at the 3-position of the chroman moiety seemed necessary for antagonism at the 5-HT1A receptor. Branched linkers seemed to impart antagonism even as racemates, however, potency of these analogues in the functional assay was not desirable enough to further pursue these compounds.

  DOI：

  10.1021/jm8007097
• 作为产物：
  描述：

  3-aminochromane-5-carboxamide 、 3-(5-fluoro-1H-indol-3-yl)propanal 在 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以42%的产率得到3-{[3-(5-fluoro-1H-indol-3-yl)propyl]amino}chromane-5-carboxamide hydrochloride
  参考文献：
  名称：

  Advances toward New Antidepressants with Dual Serotonin Transporter and 5-HT_1A Receptor Affinity within a Class of 3-Aminochroman Derivatives. Part 2

  摘要：

  Novel compounds combining a 5-HT1A moiety (3-aminochroman scaffold) and a 5-HT transporter (indole analogues) linked through,a common basic nitrogen via an alkyl chain attached at the 1- or 3-position of the indole were evaluated for dual affinity at both the 5-HT reuptake site and the 5-HT1A receptor. Compounds of most interest were found to have a 5-carbamoyl-8-fluoro-3-amino-3,4-dihydro-2H-1-benzopyran linked to a 3-alkylindole (straight chain), more specifically substituted with a 5-fluoro ((R)-(-)-35c), 5-cyano ((-)-52a), or 5,7-difluoro ((-)-52g). Several factors contributed to 5-HT1A affinity, serotonin rat transporter affinity, and functional antagonism in vitro. Although most of our analogues showed good to excellent affinities at both targets, specific features such as cyclobutyl substitution on the basic nitrogen and stereochemistry at the 3-position of the chroman moiety seemed necessary for antagonism at the 5-HT1A receptor. Branched linkers seemed to impart antagonism even as racemates, however, potency of these analogues in the functional assay was not desirable enough to further pursue these compounds.

  DOI：

  10.1021/jm8007097

文献信息

• [EN] 3-AMINO CHOMAN AND 2-AMINO TETRALIN DERIVATIVES<br/>[FR] DERIVES 3-AMINO CHOMANE ET 2-AMINO TETRALINE
  申请人：WYETH CORP

  公开号：WO2005012291A1

  公开（公告）日：2005-02-10

  3-Amino chroman and 2-amino tetralin derivatives and compositions containing such compounds are disclosed. Methods of using the 3-amino chroman and 2-amino tetralin compounds and compositions containing such compounds in the treatment of serotonin disorders, such as depression and anxiety, are also disclosed.

  揭示了3-氨基色苷和2-氨基四氢萘衍生物以及含有这些化合物的组合物。还揭示了在治疗血清素失调症，如抑郁症和焦虑症中使用3-氨基色苷和2-氨基四氢萘化合物以及含有这些化合物的组合物的方法。
• 3-Amino chroman and 2-amino tetralin derivatives
  申请人：Hatzenbuhler Theriault Nicole

  公开号：US20050032873A1

  公开（公告）日：2005-02-10

  3-Amino chroman and 2-amino tetralin derivatives and compositions containing such compounds are disclosed. Methods of using the 3-amino chroman and 2-amino tetralin compounds and compositions containing such compounds in the treatment of serotonin disorders, such as depression and anxiety, are also disclosed.

  本文披露了3-氨基色满和2-氨基四氢萘衍生物及含有这些化合物的组合物。还披露了使用3-氨基色满和2-氨基四氢萘化合物及含有这些化合物的组合物治疗血清素失调症，如抑郁和焦虑的方法。
• 3-AMINO CHROMAN AND 2-AMINO TETRALIN DERIVATIVES
  申请人：Wyeth

  公开号：EP1651637A1

  公开（公告）日：2006-05-03
• JP2007500718A
  申请人：——

  公开号：JP2007500718A

  公开（公告）日：2007-01-18