trans-2-(2-fluorophenyl)cyclopropan-1-amine hydrochloride | 131844-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: trans-2-(2-fluorophenyl)cyclopropan-1-amine hydrochloride
• 英文别名: trans-2-(2-fluorophenyl)cyclopropylamine hydrochloride；rac-(1R,2S)-2-(2-fluorophenyl)cyclopropan-1-amine hydrochloride；(1R,2S)-2-(2-fluorophenyl)cyclopropan-1-amine;hydrochloride
• CAS: 131844-47-8
• 化学式: C₉H₁₀FN*ClH
• mdl: MFCD28118783
• 分子量: 187.644
• InChiKey: FTBWFKALQNGCQS-DKXTVVGFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.48
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  26
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-碘代丙烷 、 trans-2-(2-fluorophenyl)cyclopropan-1-amine hydrochloride 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 96.0h， 以41%的产率得到(1S,2R)-2-(2-fluorophenyl)-N,N-dipropylcyclopropan-1-amine
  参考文献：
  名称：

  trans-2-Aryl-N,N-dipropylcyclopropylamines:  Synthesis and Interactions with 5-HT_1A Receptors

  摘要：

  Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [H-3]-8-OH-DPAT from rat brain 5-HT1A receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7I) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT1A receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT1A receptor affinity. The racemic mixtures of the interesting 7j and 7I were resolved into the enantiomers; 7j and 7I exhibited a high enantiomeric 5-HT1A receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7I were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (LR,2R)-7j behaved as a partial agonist whereas (1R,2S)-7I appeared as an efficacious 5-HT1A receptor agonist, stimulating both autoreceptors and postsynaptic receptors.

  DOI：

  10.1021/jm9507136
• 作为产物：
  描述：

  2-氟碘苯 在 盐酸 、 palladium diacetate 、 sodium hydroxide 、 叠氮磷酸二苯酯 、 四丁基氯化铵 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.5h， 生成 trans-2-(2-fluorophenyl)cyclopropan-1-amine hydrochloride
  参考文献：
  名称：

  trans-2-Aryl-N,N-dipropylcyclopropylamines:  Synthesis and Interactions with 5-HT_1A Receptors

  摘要：

  Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [H-3]-8-OH-DPAT from rat brain 5-HT1A receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7I) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT1A receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT1A receptor affinity. The racemic mixtures of the interesting 7j and 7I were resolved into the enantiomers; 7j and 7I exhibited a high enantiomeric 5-HT1A receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7I were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (LR,2R)-7j behaved as a partial agonist whereas (1R,2S)-7I appeared as an efficacious 5-HT1A receptor agonist, stimulating both autoreceptors and postsynaptic receptors.

  DOI：

  10.1021/jm9507136

文献信息

• C–H activation enables a rapid structure–activity relationship study of arylcyclopropyl amines for potent and selective LSD1 inhibitors
  作者：Shin Miyamura、Misaho Araki、Yosuke Ota、Yukihiro Itoh、Shusuke Yasuda、Mitsuharu Masuda、Tomoyuki Taniguchi、Yoshihiro Sowa、Toshiyuki Sakai、Takayoshi Suzuki、Kenichiro Itami、Junichiro Yamaguchi

  DOI：10.1039/c6ob01483f

  日期：——

  Potent and selective LSD1 inhibitors were synthesized rapidly by a C–H borylation and cross-coupling sequence.

  通过C-H硼化和交叉偶联序列，快速合成了有效且选择性的LSD1抑制剂。
• CYCLOPROPYLAMINES AS LSD1 INHIBITORS
  申请人：INCYTE CORPORATION

  公开号：US20150225401A1

  公开（公告）日：2015-08-13

  The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

  本发明涉及环丙胺衍生物，其为LSD1抑制剂，可用于治疗癌症等疾病。
• Cyclopropylamines as LSD1 inhibitors
  申请人：Incyte Corporation

  公开号：US10174030B2

  公开（公告）日：2019-01-08

  The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.

  本发明涉及环丙胺衍生物，它们是治疗癌症等疾病的 LSD1 抑制剂。
• Structure–Activity Relationship and <i>In Silico</i> Evaluation of <i>cis</i>- and <i>trans</i>-PCPA-Derived Inhibitors of LSD1 and LSD2
  作者：Hideaki Niwa、Chiduru Watanabe、Shin Sato、Toshiyuki Harada、Hisami Watanabe、Ryo Tabusa、Shunsuke Fukasawa、Ayane Shiobara、Tomoko Hashimoto、Osamu Ohno、Kana Nakamura、Keiko Tsuganezawa、Akiko Tanaka、Mikako Shirouzu、Teruki Honma、Kenji Matsuno、Takashi Umehara

  DOI：10.1021/acsmedchemlett.2c00294

  日期：2022.9.8
• CYCLOPROPYLAMINES FOR USE AS LSD1 INHIBITORS
  申请人：Incyte Corporation

  公开号：EP3626713B1

  公开（公告）日：2021-09-29