(4R)-4-(二丙基氨基)-1,3,4,5-四氢苯并[cd]吲哚-6-甲酰胺 | 115994-31-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: (4R)-4-(二丙基氨基)-1,3,4,5-四氢苯并[cd]吲哚-6-甲酰胺
• 英文名称: LY 228729
• 英文别名: (-)-4-(R)-(dipropylamino)-1,3,4,5-tetrahydrobenz[cd]indole-6-carboxamide；(-)-4-(Dipropylamino)-1,3,4,5-tetrahydrobenz-{c,d}-indole-6-carboxamide；Benz(cd)indole-6-carboxamide, 4-(dipropylamino)-1,3,4,5-tetrahydro-, (R)-；(4R)-4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indole-6-carboxamide
• CAS: 115994-31-5
• 化学式: C₁₈H₂₅N₃O
• 分子量: 299.416
• InChiKey: YTOJFUORFUYGSV-ZDUSSCGKSA-N

物化性质

• 熔点：
  178-180 °C
• 沸点：
  510.1±50.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  62.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-benzoyl-4,5-epoxy-1,2,2a,3,4,5-hexahydrobenzindole 在 palladium on activated charcoal manganese(IV) oxide 、 氢氧化钾 、 sodium hydroxide 、 磷酸 、 氨 、 氢气 、 碘 、 potassium carbonate 、 钯 、 过碘酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 溶剂黄146 、 甲苯 、 乙腈 、 正丁醇 为溶剂， -10.0~100.0 ℃ 、101.33 kPa 条件下， 反应 71.5h， 生成 (4R)-4-(二丙基氨基)-1,3,4,5-四氢苯并[cd]吲哚-6-甲酰胺
  参考文献：
  名称：

  Synthetic Studies toward the Partial Ergot Alkaloid LY228729, a Potent 5HT_1A Receptor Agonist

  摘要：

  Synthetic studies on LY228729 (3) afforded two innovative approaches for the construction of this class of partial ergoline 5HT(1a) receptor agonists. The first synthesis is based upon a diastereoselective epoxidation of racemic olefin 5, followed by ring opening and covalent resolution to furnish the key amino alcohol 8. Aziridination of amino alcohol 8, with subsequent tandem hydrogenolysis of the benzylic aziridine and auxiliary bonds, provided access to the optically active primary amine 13. A novel catalytic carboxamidation reaction installed the requisite side chain, Alternatively, the chiral pool was drawn upon for the single stereogenic center by virtue of L-tryptophan, albeit by a more circuitous route than expected. L-Tryptophan was differentially protected and reduced to the indoline diastereomers 26a,b which were separated by fractional crystallization. The two indoline diastereoisomers were independently cyclized by a Friedel-Crafts protocol, which under thermodynamic control afforded enantiomeric ketones 30a. The ketone was deoxygenated with a two-step reduction protocol to intersect the initial route and complete the second total synthesis. The two routes offer complementary access to this exciting class of partial ergot alkaloids.

  DOI：

  10.1021/jo971256z

文献信息

• The synthesis of carbon-14 labeled (R)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz[cd]indole-6-carboxamide hippurate. A partial ergoline with 5-HT1A agonist activity and an125I-labeled analog
  作者：William J. Wheeler、Steven P. Swanson、David L. Varie、Douglas D. O'Bannon

  DOI：10.1002/jlcr.907

  日期：2005.2

  Partial ergoline agonists such as (R)-4-(dipropylamino)-1,3,4,5-tetrahydrobenz[cd]-indole-6-carboxamide (LY228729, 1a) mimic a locked conformational analog of serotonin and in fact possess potent in vitro activity as agonists of the 5-HT1A receptor. In the course of pre-clinical investigation of 1a for potential use as an anxiolytic agent, 1b was prepared in a five step synthesis from K14CN. In addition

  部分麦角碱激动剂，如 (R)-4-(二丙氨基)-1,3,4,5-四氢苯并[cd]-吲哚-6-甲酰胺 (LY228729, 1a) 模拟血清素的锁定构象类似物，实际上具有有效的作为 5-HT1A 受体激动剂的体外活性。在 1a 潜在用作抗焦虑剂的临床前研究过程中，1b 是通过 K14CN 的五步合成制备的。此外，还制备了 1a 的 125I 类似物，以帮助开发放射免疫分析 (RIA)。版权所有 © 2005 John Wiley & Sons, Ltd.
• Crystalline salt of 4-(di-n-propyl)amino-6-aminocarbonyl-1,3,4,5-tetrahydrobenz[cd]indole
  申请人：ELI LILLY AND COMPANY

  公开号：EP0444852A2

  公开（公告）日：1991-09-04

  4-(Di-n-propyl)amino-6-aminocarbonyl-1,3,4,5-tetrahydrobenz[cd]indole hippurate and its method of preparation and use are provided.

  本发明提供了 4-(二正丙基)氨基-6-氨基甲酰基-1,3,4,5-四氢苯并[cd]吲哚海波酸盐及其制备方法和用途。
• Fast-dispersing dosage form containing 5-HT1 agonists
  申请人：——

  公开号：US20040023948A1

  公开（公告）日：2004-02-05

  This invention relates to a pharmaceutical composition for oral administration comprising a carrier and, as an active ingredient, a 5-HT 1 agonist, characterized in that the composition is formulated to reduce pre-systemic metabolism of said 5-HT 1 agonist. A process for preparing such a composition and the use of such a composition for the treatment of anxiety, depression, attention deficit disorder and/or panic disorders and/or as a memory enhancer are also provided.

  本发明涉及一种口服药物组合物，该组合物由载体和作为活性成分的 5-HT 1 激动剂，其特征在于该组合物的配制可减少所述 5-HT 1 激动剂。本发明还提供了制备这种组合物的工艺以及这种组合物用于治疗焦虑症、抑郁症、注意力缺陷障碍和/或恐慌症和/或作为记忆增强剂的用途。
• The synthesis of (+)- and (−)-1-benzoyl-1,2,2a,3,4,5-hexahydrobenz[cd]indol-4-amine, and preparation of LY228729.
  作者：Michael J. Martinelli、M. Robert Leanna、David L. Varie、Barry C. Peterson、Thomas J. Kress、James P. Wepsiec、Vien V. Khau

  DOI：10.1016/s0040-4039(00)97303-9

  日期：——

  Racemic epoxide 5 was reacted with S-Phenylethylamine to afford diastereomers 6 and 7, from which amino alcohol 6 could be isolated directly. Aziridine formation and tandem-hydrogenolysis provided optically pure primary amine 2 (31% from racemic 4), which was further elaborated to LY228729 (15), an interesting 5HT1a receptor agonist.
• US5397799A
  申请人：——

  公开号：US5397799A

  公开（公告）日：1995-03-14