8-fluoro-5-methoxychroman-3-amine | 170483-03-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-fluoro-5-methoxychroman-3-amine
• 英文别名: 3-Amino-8-fluoro-5-methoxychroman；(8-fluoro-5-methoxy-3,4-dihydro-2H-chromen-3-yl)amine；8-fluoro-5-methoxy-3,4-dihydro-2H-chromen-3-amine
• CAS: 170483-03-1
• 化学式: C₁₀H₁₂FNO₂
• 分子量: 197.209
• InChiKey: WZOULZLGSKBYTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-fluoro-5-methoxychroman-3-amine 、 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87%的产率得到8-fluoro-N-[3-(5-fluoro-1H-indol-3-yl)propyl]-5-methoxychroman-3-amine
  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：

  8-Fluoro-5-methoxychroman-3-yl carbamic acid benzyl ester 在 palladium on activated carbon 作用下， 以 乙醇 、 氢气 、 溶剂黄146 、 甲苯 为溶剂， 生成 8-fluoro-5-methoxychroman-3-amine
  参考文献：
  名称：

  Chroman derivatives

  摘要：

  本文披露了3-氨基-5-氨基甲酰基色苷和8-氟-3-氨基-5-氨基甲酰基色苷，以及它们的对映体和盐。还披露了含有这些化合物作为活性成分的药物组合物。这些化合物在治疗中枢神经系统的5-羟色胺介导的疾病中是有用的。

  公开号：

  US05420151A1

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。
• [EN] NOVEL (R)-5-CARBAMOYL-8-FLUORO-3-N,N-DISUBSTITUTED-AMINO-3,4-DIHYDRO-2H-1-BENZOPYRANES<br/>[FR] NOUVEAUX (R)-5-CARBAMYL-8-FLUORO-3-AMINO N,N DISUBSTITUES-3,4-DIHYDRO-2H-1-BENZOPYRANNES
  申请人：ASTRA AKTIEBOLAG

  公开号：WO1995011891A1

  公开（公告）日：1995-05-04

  (EN) Compounds of general formula (I), wherein R1 is n-propyl or cyclobutyl; R2 is isopropyl, tertiary butyl, cyclobutyl, cyclopentyl or cyclohexyl; R3 is hydrogen; R4 is hydrogen or methyl; as (R)-enantiomer and in the form of free base or pharmaceutically acceptable salts thereof, process for their preparation, pharmaceutical composition, use of and method of treatment of disorders in CNS.(FR) Sont décrits des composés de formule générale (I) où R1 est n-propyle ou cyclobutyle; R2 est isopropyle, butyle tertiaire, cyclobutyle, cyclopentyle ou cyclohéxyle; R3 est hydrogène; R4 est hydrogène ou méthyle; se présentant sous forme de (R)-énantiomères et de bases libres ou bien de sels pharmaceutiquement acceptables; un procédé pour leur préparation, une composition pharmaceutique, leur utilisation et un procédé de traitement de troubles du système nerveux central.

  化合物的一般式(I)，其中R1是正丙基或环丁基；R2是异丙基，三级丁基，环丁基，环戊基或环己基；R3是氢；R4是氢或甲基；以(R)-对映体的形式和作为自由碱或药学上可接受的盐，制备它们的过程，制药组合物，用途和治疗中枢神经系统疾病的方法。
• Method for the treatment of migraine
  申请人：Astra Aktiebolag

  公开号：US05639784A1

  公开（公告）日：1997-06-17

  A method is disclosed for the treatment of migraine by the administration of 3-amino-5-carbamoyl-chromans and 8-fluoro-3-amino-5-carbamoylchromans or enantiomers or salts thereof.

  本发明揭示了一种通过给予3-氨基-5-氨甲酰基-色酮和8-氟-3-氨基-5-氨甲酰基色酮或其对映体或盐来治疗偏头痛的方法。
• Method for the treatment of depression
  申请人：Astra Aktiebolag

  公开号：US05641807A1

  公开（公告）日：1997-06-24

  A method is disclosed for the treatment of depression by the administration of 3-amino-5-carbamoylchromans and 8-fluoro-3-amino-5-carbamoylchromans or enantiomers or salts thereof.

  本发明公开了一种通过给予3-氨基-5-氨甲酰基色酮和8-氟-3-氨基-5-氨甲酰基色酮或其对映体或盐来治疗抑郁症的方法。
• Intermediates in the synthesis of chroman derivatives
  申请人：Astra Aktiebolag

  公开号：US05646309A1

  公开（公告）日：1997-07-08

  Compounds of the formula ##STR1## are disclosed. These compounds are employed as intermediates in the synthesis of aminochroman compounds useful in the treatment of CNS disorders.

  公式为 ##STR1## 的化合物已被披露。这些化合物被用作合成氨基色酮化合物的中间体，这些化合物在治疗中枢神经系统疾病方面是有用的。