N,N-dibenzyl-2-(1-methyl-1H-indol-3-yl)ethanamine | 102951-77-9

• 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: N,N-dibenzyl-2-(1-methyl-1H-indol-3-yl)ethanamine
• 英文别名: N,N-dibenzyl-2-(1-methyl-1H-indol-3-yl)ethan-1-amine；1-Methyl-3-(2-dibenzylamino-ethyl)-indol；dibenzyl-[2-(1-methyl-indol-3-yl)-ethyl]-amine；1-Methyl-N,N-dibenzyl-tryptamine；N,N-dibenzyl-2-(1-methylindol-3-yl)ethanamine
• CAS: 102951-77-9
• 化学式: C₂₅H₂₆N₂
• 分子量: 354.495
• InChiKey: LRHCLVBJKHJVFW-UHFFFAOYSA-N

物化性质

• 熔点：
  123-124 °C
• 沸点：
  509.9±38.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  8.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N,N-dibenzyl-2-(1-methyl-1H-indol-3-yl)ethanamine 在 N-溴代丁二酰亚胺(NBS) 、 叔丁基锂 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  通过Bischler-Napieralski / Semipinacol重排反应的发展来合成Aspidofractinine生物碱的集体总合成。

  摘要：

  已经开发了串联的Bischler–Napieralski / semipinacol重排反应，目的是组装双（螺环）吲哚骨架（天冬氨酸吗啡型单萜吲哚生物碱的优先结构单元），并与随后的Mannich反应结合使用，以快速构建这些具有连续四元中心的分子的中心桥联双环[2.2.1]庚烷环系统。这种新策略的发展最终导致了四种aspaspfractinine生物碱的总全合成。

  DOI：

  10.1002/anie.202009238
• 作为产物：
  描述：

  色胺 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 N,N-dibenzyl-2-(1-methyl-1H-indol-3-yl)ethanamine
  参考文献：
  名称：

  Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity

  摘要：

  TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N,N'-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC50 0.2 +/- 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an lcilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1 - 1 mu g s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the SI-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.

  DOI：

  10.1021/acs.jmedchem.8b00545

文献信息

• Indole derivatives and anti-ulcer compositions thereof
  申请人：Nisshin Flour Milling Co., Ltd.

  公开号：US05252580A1

  公开（公告）日：1993-10-12

  Disclosed are indole derivatives of formula (I) ##STR1## wherein Y represents H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or halogen; Z represents --CH.sub.2 N(R.sub.5)--; R represents H or --CH.sub.2 CH.sub.2 X where X represents pyridyl, aralkyloxy or substituted amino of NR.sub.6 R.sub.7 where R.sub.6 represents H, C.sub.1 -C.sub.6 alkyl, aralkyl, C.sub.1 -C.sub.6 alkoxycarbonyl, aralkyloxycarbonyl or halogenated C.sub.1 -C.sub.6 alkoxycarbonyl and R.sub.7 represents H, C.sub.1 -C.sub.6 alkyl or aralkyl, or together with R.sub.2 may form a ring of --(CH.sub.2).sub.n -- (n is 1-4) or ##STR2## R.sub.1 represents H, C.sub.1 -C.sub.6 alkyl, aralkyl or arylsulfonyl; R.sub.2 represents C.sub.1 -C.sub.6 alkyl, hydroxy, C.sub.1 -C.sub.6 alkoxy or aralkyloxy; R.sub.3 represents H, C.sub.1 -C.sub.6 alkyl, aralkyl or halogenated C.sub.1 -C.sub.6 alkyl; R.sub.4 and R.sub.5 may be the same or different and each represents H, C.sub.1 -C.sub.6 alkyl or aralkyl or both may together form a ring of --(CH.sub.2).sub.m -- (m is 3 or 4); or pharmaceutically acceptable acid addition salts thereof. They are useful as an antiulcer agent.

  本发明涉及公式（I）的吲哚衍生物##STR1##其中Y代表H，C.sub.1 -C.sub.6烷基，C.sub.1 -C.sub.6烷氧基或卤素；Z代表--CH.sub.2 N(R.sub.5)--；R代表H或--CH.sub.2 CH.sub.2 X，其中X代表吡啶基，芳基氧基或NR.sub.6 R.sub.7的取代氨基，其中R.sub.6代表H，C.sub.1 -C.sub.6烷基，芳基烷基，C.sub.1 -C.sub.6烷氧羰基，芳基氧羰基或卤代C.sub.1 -C.sub.6烷氧羰基，R.sub.7代表H，C.sub.1 -C.sub.6烷基或芳基烷基，或与R.sub.2一起形成--(CH.sub.2).sub.n --（n为1-4）的环或##STR2##R.sub.1代表H，C.sub.1 -C.sub.6烷基，芳基烷基或芳基磺酰基；R.sub.2代表C.sub.1 -C.sub.6烷基，羟基，C.sub.1 -C.sub.6烷氧基或芳基氧基；R.sub.3代表H，C.sub.1 -C.sub.6烷基，芳基烷基或卤代C.sub.1 -C.sub.6烷基；R.sub.4和R.sub.5可以相同也可以不同，每个代表H，C.sub.1 -C.sub.6烷基或芳基烷基，或两者一起形成--(CH.sub.2).sub.m --（m为3或4）的环；或其药学上可接受的酸盐。它们可用作抗溃疡剂。
• β‐C−H Allylation of Trialkylamines with Allenes Promoted by Synergistic Borane/Palladium Catalysis
  作者：Ming Zhang、Zi‐Lu Tang、Heng Luo、Xiao‐Chen Wang

  DOI：10.1002/anie.202317610

  日期：2024.1.25

  The β-C−H allylation reactions of trialkylamines with allenes were accomplished by a synergistic borane/palladium catalysis. The borane and palladium catalysts promoted the formation of an enamine intermediate from a trialkylamine and a palladium-π-allyl intermediate from an allene, respectively.

  三烷基胺与丙二烯的 β-C−H 烯丙基化反应是通过硼烷/钯的协同催化完成的。硼烷和钯催化剂分别促进从三烷基胺形成烯胺中间体和从丙二烯形成钯-π-烯丙基中间体。
• Indole derivatives and anti-ulcer compositions
  申请人：NISSHIN FLOUR MILLING CO., LTD.

  公开号：EP0535529A2

  公开（公告）日：1993-04-07

  Disclosed are indole derivatives of formula (I) wherein    Y represents H, C⁵-C¼ alkyl, C⁵-C¼ alkoxy or halogen;    Z represents -CH⁶N(Rψ)-;    R represents H or -CH⁶CH⁶X where X represents pyridyl, aralkyloxy or substituted amino of NR¼R½ where R¼ represents H, C⁵-C¼ alkyl, aralkyl, C⁵-C¼ alkoxycarbonyl, aralkyloxycarbonyl or halogenated C⁵-C¼ alkoxycarbonyl and R½ represents H, C⁵-C¼ alkyl or aralkyl, or together with R⁶ may form a ring of -(CH⁶)n- (n is 1-4) or    R⁵ represents H, C⁵-C¼ alkyl, aralkyl or arylsulfonyl;    R⁶ represents C⁵-C¼ alkyl, hydroxy, C⁵-C¼ alkoxy or aralkyloxy;    R⁷ represents H, C⁵-C¼ alkyl, aralkyl or halogenated C⁵-C¼ alkyl;    R⁸ and Rψ may be the same or different and each represents H, C⁵-C¼ alkyl or aralkyl or both may together form a ring of -(CH⁶)m- (m is 3 or 4); or pharmaceutically acceptable acid addition salts thereof. They are useful as an antiulcer agent.

  公开了式 (I) 的吲哚衍生物 其中 Y 代表 H、C⁵-C¼ 烷基、C⁵-C¼ 烷氧基或卤素； Z 代表-CH⁶N(Rψ)-； R 代表 H 或-CH⁶CH⁶X，其中 X 代表吡啶基、烷氧基或 NR¼R½ 的取代氨基，其中 R¼ 代表 H、C⁵-C¼ 烷基、烷芳基、C⁵-C¼ 烷氧基羰基或烷氧羰基、R½代表 H、C⁵-C¼ 烷基或芳烷基，或与 R⁶ 一起可形成-(CH⁶)n-（n 为 1-4）环，或 R⁵ 代表 H、C⁵-C¼ 烷基、芳烷基或芳磺酰基； R⁶ 代表 C⁵-C¼ 烷基、羟基、C⁵-C¼ 烷氧基或芳氧基； R⁷ 代表 H、C⁵-C¼ 烷基、芳烷基或卤代 C⁵-C¼ 烷基； R⁸和Rψ可以相同或不同，各自代表H、C⁵-C¼烷基或芳烷基，或两者可共同形成-(CH⁶)m- (m为3或4)的环； 或其药学上可接受的酸加成盐。它们可用作抗溃疡剂。
• Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity
  作者：Alessia Bertamino、Nunzio Iraci、Carmine Ostacolo、Paolo Ambrosino、Simona Musella、Veronica Di Sarno、Tania Ciaglia、Giacomo Pepe、Marina Sala、Maria Virginia Soldovieri、Ilaria Mosca、Sara Gonzalez-Rodriguez、Asia Fernandez-Carvajal、Antonio Ferrer-Montiel、Ettore Novellino、Maurizio Taglialatela、Pietro Campiglia、Isabel Gomez-Monterrey

  DOI：10.1021/acs.jmedchem.8b00545

  日期：2018.7.26

  TRPM8 has been implicated in nociception and pain and is currently regarded as an attractive target for the pharmacological treatment of neuropathic pain syndromes. A series of analogues of N,N'-dibenzyl tryptamine 1, a potent TRPM8 antagonist, was prepared and screened using a fluorescence-based in vitro assay based on menthol-evoked calcium influx in TRPM8 stably transfected HEK293 cells. The tryptophan derivative 14 was identified as a potent (IC50 0.2 +/- 0.2 nM) and selective TRPM8 antagonist. In vivo, 14 showed significant target coverage in both an lcilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1 - 1 mu g s.c.) mice models. Molecular modeling studies identified the putative binding mode of these antagonists, suggesting that they could influence an interaction network between the SI-4 transmembrane segments and the TRP domains of the channel subunits. The tryptophan moiety provides a new pharmacophoric scaffold for the design of highly potent modulators of TRPM8-mediated pain.
• US5252580A
  申请人：——

  公开号：US5252580A

  公开（公告）日：1993-10-12