tert-butyl 5-fluoro-3-(3-{[(3R)-8-fluoro-5-(methylcarbamoyl)-3,4-dihydro-2H-chromen-3-yl](propyl)amino}propyl)-1H-indole-1-carboxylate | 1073593-27-7

• 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: tert-butyl 5-fluoro-3-(3-{[(3R)-8-fluoro-5-(methylcarbamoyl)-3,4-dihydro-2H-chromen-3-yl](propyl)amino}propyl)-1H-indole-1-carboxylate
• 英文别名: tert-butyl 5-fluoro-3-[3-[[(3R)-8-fluoro-5-(methylcarbamoyl)-3,4-dihydro-2H-chromen-3-yl]-propylamino]propyl]indole-1-carboxylate
• CAS: 1073593-27-7
• 化学式: C₃₀H₃₇F₂N₃O₄
• 分子量: 541.638
• InChiKey: IMBLFHNLCOUOIV-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 5-fluoro-3-(3-{[(3R)-8-fluoro-5-(methylcarbamoyl)-3,4-dihydro-2H-chromen-3-yl](propyl)amino}propyl)-1H-indole-1-carboxylate 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以100%的产率得到(3R)-(-)-8-fluoro-3-{[3-(5-fluoro-1H-indol-3-yl)propyl](propyl)amino}-N-methylchromane-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
• 作为产物：
  描述：

  tert-butyl 3-{3-[{(3R)-5-[bis(tert-butoxycarbonyl)carbamoyl]-8-fluoro-3,4-dihydro-2H-chromen-3-yl}(propyl)amino]propyl}-5-fluoro-1H-indole-1-carboxylate 、 甲胺 以 四氢呋喃 为溶剂， 以62%的产率得到tert-butyl 3-{3-[{(3R)-5-[(tert-butoxycarbonyl)carbamoyl]-8-fluoro-3,4-dihydro-2H-chromen-3-yl}(propyl)amino]propyl}-5-fluoro-1H-indole-1-carboxylate
  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

• Advances toward New Antidepressants with Dual Serotonin Transporter and 5-HT_1A Receptor Affinity within a Class of 3-Aminochroman Derivatives. Part 2
  作者：Nicole T. Hatzenbuhler、Reinhardt Baudy、Deborah A. Evrard、Amedeo Failli、Boyd L. Harrison、Steven Lenicek、Richard E. Mewshaw、Annmarie Saab、Uresh Shah、Jean Sze、Minsheng Zhang、Dahui Zhou、Michael Chlenov、Michael Kagan、Jeannette Golembieski、Geoffrey Hornby、Margaret Lai、Deborah L. Smith、Kelly M. Sullivan、Lee E. Schechter、Terrance H. Andree

  DOI：10.1021/jm8007097

  日期：2008.11.13

  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.