tert-butyl {2-[(5-amino-2,3-dihydro-1-benzofuran-4-yl)amino]ethyl}carbamate | 1309752-65-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: tert-butyl {2-[(5-amino-2,3-dihydro-1-benzofuran-4-yl)amino]ethyl}carbamate
• 英文别名: tert-butyl (2-((5-amino-2,3-dihydrobenzofuran-4-yl)amino)ethyl)carbamate；tert-butyl N-[2-[(5-amino-2,3-dihydro-1-benzofuran-4-yl)amino]ethyl]carbamate
• CAS: 1309752-65-5
• 化学式: C₁₅H₂₃N₃O₃
• 分子量: 293.366
• InChiKey: ADLULGUICPPQES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  85.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl {2-[(5-amino-2,3-dihydro-1-benzofuran-4-yl)amino]ethyl}carbamate 在 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.5h， 生成 2-(2-methoxy-7,8-dihydro-1H-benzofuran[4,5-d]imidazol-1-yl)ethanamine
  参考文献：
  名称：

  [EN] COMPOUNDS, PROCESS FOR OBTAINING THE COMPOUNDS, PHARMACEUTICAL COMPOSITION, USE OF THE COMPOUNDS AND METHOD FOR TREATING PSYCHIATRIC DISORDERS AND/OR SLEEP DISORDERS
  [FR] COMPOSÉS, PROCÉDÉ D'OBTENTION DES COMPOSÉS, COMPOSITION PHARMACEUTIQUE, UTILISATION DES COMPOSÉS ET PROCÉDÉ DE TRAITEMENT DE TROUBLES PSYCHIATRIQUES ET/OU DE TROUBLES DU SOMMEIL

  摘要：

  本发明涉及一种新颖和创新的药理活性苯并咪唑衍生物化合物，这些化合物出人意料地具有高亲和力的褪黑激素MT1和MT2受体，并对CYP450复合酶f，特别是CYP1A2具有低亲和力。本发明还涉及这些化合物的新颖和创新的合成途径，包括这些化合物的药物组合物和将这些化合物用于治疗受精神障碍和/或与这些受体相关的睡眠障碍的个体（特别是抑郁症、焦虑症、昼夜节律紊乱），以及生产该组合物的方法。

  公开号：

  WO2018076090A1
• 作为产物：
  描述：

  2,6-二氟苯乙酸 在 lithium aluminium tetrahydride 、 lithium hydroxide monohydrate 、 硫酸 、 palladium 10% on activated carbon 、 水 、 氢气 、 硝酸 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.5h， 生成 tert-butyl {2-[(5-amino-2,3-dihydro-1-benzofuran-4-yl)amino]ethyl}carbamate
  参考文献：
  名称：

  Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-c]pyrazolo[1,5-a]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands

  摘要：

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.

  DOI：

  10.1021/jm200385u

文献信息

• [EN] COMPOUNDS, PROCESS FOR OBTAINING THE COMPOUNDS, PHARMACEUTICAL COMPOSITION, USE OF THE COMPOUNDS AND METHOD FOR TREATING PSYCHIATRIC DISORDERS AND/OR SLEEP DISORDERS<br/>[FR] COMPOSÉS, PROCÉDÉ D'OBTENTION DES COMPOSÉS, COMPOSITION PHARMACEUTIQUE, UTILISATION DES COMPOSÉS ET PROCÉDÉ DE TRAITEMENT DE TROUBLES PSYCHIATRIQUES ET/OU DE TROUBLES DU SOMMEIL
  申请人：ACHE LABORATORIOS FARMACEUTICOS SA

  公开号：WO2018076090A1

  公开（公告）日：2018-05-03

  The present invention relates to novel and inventive pharmacologically active benzimidazole derivative compounds, which surprisingly have high affinity for melatonin MTi and MT2 receptors and low affinity for CYP450 complex enzymes f specially CYP1A2. The present, invention also relates to novel and inventive routes of synthesis of these compounds, pharmaceutical compositions comprising the compounds and the use of these compounds in the treatment of individuais affected by psychiatric disorders and/or sleep disorders related to these receptors (specially depression, anxiety, circadian cycle disorders), in addition to process for producing the composition.

  本发明涉及一种新颖和创新的药理活性苯并咪唑衍生物化合物，这些化合物出人意料地具有高亲和力的褪黑激素MT1和MT2受体，并对CYP450复合酶f，特别是CYP1A2具有低亲和力。本发明还涉及这些化合物的新颖和创新的合成途径，包括这些化合物的药物组合物和将这些化合物用于治疗受精神障碍和/或与这些受体相关的睡眠障碍的个体（特别是抑郁症、焦虑症、昼夜节律紊乱），以及生产该组合物的方法。
• COMPOUNDS, PROCESS FOR OBTAINING THE COMPOUNDS, PHARMACEUTICAL COMPOSITION, USE OF THE COMPOUNDS AND METHOD FOR TREATING PSYCHIATRIC DISORDERS AND/OR SLEEP DISORDERS
  申请人：Aché Laboratórios Farmacêuticos S.A.

  公开号：EP3741760A1

  公开（公告）日：2020-11-25

  The present invention relates to novel and inventive pharmacologically active benzimidazole derivative compounds, which surprisingly have high affinity for melatonin MT1 and MT2 receptors and low affinity for CYP450 complex enzymes, specially CYP1A2. The present invention also relates to novel and inventive routes of synthesis of these compounds, pharmaceutical compositions comprising the compounds and the use of these compounds in the treatment of individuals affected by psychiatric disorders and/or sleep disorders related to these receptors (specially depression, anxiety, circadian cycle disorders), in addition to process for producing the composition.

  本发明涉及具有药理活性的新型和创造性的苯并咪唑衍生物化合物，令人惊讶的是，这些化合物对褪黑素MT1和MT2受体具有高亲和力，而对CYP450复合酶，特别是CYP1A2具有低亲和力。本发明还涉及这些化合物的新颖和创造性的合成路线、包含这些化合物的药物组合物以及这些化合物在治疗与这些受体有关的精神障碍和/或睡眠障碍（特别是抑郁症、焦虑症、昼夜节律紊乱）患者中的用途，此外还涉及组合物的生产工艺。
• Compounds, process for obtaining the compounds, pharmaceutical composition, use of the compounds and method for treating psychiatric disorders and/or sleep disorders
  申请人：ACHÉ LABORATÓRIOS FARMACÊUTICOS S.A.

  公开号：US10781182B2

  公开（公告）日：2020-09-22

  The present invention relates to novel and inventive pharmacologically active benzimidazole derivative compounds, which surprisingly have high affinity for melatonin MT1 and MT2 receptors and low affinity for CYP450 complex enzymes, specially CYP1A2. The present invention also relates to novel and inventive routes of synthesis of these compounds, pharmaceutical compositions comprising the compounds and the use of these compounds in the treatment of individuals affected by psychiatric disorders and/or sleep disorders related to these receptors (specially depression, anxiety, circadian cycle disorders), in addition to process for producing the composition.

  本发明涉及具有药理活性的新型和创造性的苯并咪唑衍生物化合物，令人惊讶的是，这些化合物对褪黑素MT1和MT2受体具有高亲和力，而对CYP450复合酶，特别是CYP1A2具有低亲和力。本发明还涉及这些化合物的新颖和创造性的合成路线、包含这些化合物的药物组合物以及这些化合物在治疗与这些受体有关的精神障碍和/或睡眠障碍（特别是抑郁症、焦虑症、昼夜节律紊乱）患者中的用途，此外还涉及组合物的生产工艺。
• Synthesis of a Novel Series of Tricyclic Dihydrofuran Derivatives: Discovery of 8,9-Dihydrofuro[3,2-<i>c</i>]pyrazolo[1,5-<i>a</i>]pyridines as Melatonin Receptor (MT₁/MT₂) Ligands
  作者：Tatsuki Koike、Takafumi Takai、Yasutaka Hoashi、Masaharu Nakayama、Yohei Kosugi、Masato Nakashima、Shin-ichi Yoshikubo、Keisuke Hirai、Osamu Uchikawa

  DOI：10.1021/jm200385u

  日期：2011.6.23

  Novel tricyclic dihydrofuran derivatives were designed, synthesized, and evaluated as melatonin receptor (MT1/MT2) ligands based on the previously reported 1,6-dihydro-2H-indeno[5,4-b]furan la. By screening the central tricyclic cores, we identified 8,9-dihydrofuro [3,2-c]pyrazolo [1,5-a]pyridine as a potent scaffold with a high ligand-lipophilicity efficiency (LLE) value. Subsequent optimization of the side chains led to identification of the potent MT1/MT2 agonist 4d (MT1, K-i = 0.062 nM; MT2, K-i = 0.420 nM) with good oral absorption and blood-brain barrier (BBB) penetration in rats. The oral administration of compound 4d exhibited a sleep-promoting action in freely moving cats at 0.1 mg/kg.
• Discovery of <b>ACH-000143</b>: A Novel Potent and Peripherally Preferred Melatonin Receptor Agonist that Reduces Liver Triglycerides and Steatosis in Diet-Induced Obese Rats
  作者：Marcos Antonio Ferreira、Hatylas Azevedo、Alessandra Mascarello、Natanael Dante Segretti、Elisa Russo、Valter Russo、Cristiano Ruch Werneck Guimarães

  DOI：10.1021/acs.jmedchem.0c00627

  日期：2021.2.25