(trans-4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methanamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (trans-4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methanamine
• 化学式: C₁₈H₂₇Cl₂N₃
• 分子量: 356.338
• InChiKey: IOALLYRQXBDBMB-SHTZXODSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  32.5
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (trans-4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methanamine 、 二甲氨基甲酰氯 以 二氯甲烷 为溶剂， 反应 18.0h， 以67%的产率得到3-((trans-4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methyl)-1,1-dimethylurea
  参考文献：
  名称：

  A Structure–Activity Analysis of Biased Agonism at the Dopamine D2 Receptor

  摘要：

  Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl (trans-4-(2-(3,4dihydroisoquinolin-2(1H)-yOethyl)cyclohexyl)carbamate (4). This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.

  DOI：

  10.1021/jm401318w
• 作为产物：
  描述：

  tranexamic acid 在 盐酸 、 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 1,2-二氯乙烷 、 甲苯 为溶剂， 反应 2.0h， 生成 (trans-4-((4-(2,3-dichlorophenyl)piperazin-1-yl)methyl)cyclohexyl)methanamine
  参考文献：
  名称：

  A Structure–Activity Analysis of Biased Agonism at the Dopamine D2 Receptor

  摘要：

  Biased agonism offers an opportunity for the medicinal chemist to discover pathway-selective ligands for GPCRs. A number of studies have suggested that biased agonism at the dopamine D2 receptor (D2R) may be advantageous for the treatment of neuropsychiatric disorders, including schizophrenia. As such, it is of great importance to gain insight into the SAR of biased agonism at this receptor. We have generated SAR based on a novel D2R partial agonist, tert-butyl (trans-4-(2-(3,4dihydroisoquinolin-2(1H)-yOethyl)cyclohexyl)carbamate (4). This ligand shares structural similarity to cariprazine (2), a drug awaiting FDA approval for the treatment of schizophrenia, yet displays a distinct bias toward two different signaling end points. We synthesized a number of derivatives of 4 with subtle structural modifications, including incorporation of cariprazine fragments. By combining pharmacological profiling with analytical methodology to identify and to quantify bias, we have demonstrated that efficacy and biased agonism can be finely tuned by minor structural modifications to the head group containing the tertiary amine, a tail group that extends away from this moiety, and the orientation and length of a spacer region between these two moieties.

  DOI：

  10.1021/jm401318w

文献信息

• [DE] CARBOXAMIDE DES INDOLIZINS UND SEINER AZA- UND DIAZADERIVATE<br/>[EN] INDOLIZINE CARBOXAMIDES AND THE AZA AND DIAZA DERIVATIVES THEREOF<br/>[FR] CARBOXAMIDES D'INDOLIZINE ET LEURS AZA- ET DIAZA-DERIVES
  申请人：SANOL ARZNEI SCHWARZ GMBH

  公开号：WO2006015737A1

  公开（公告）日：2006-02-16

  Die vorliegende Erfindung betrifft neurorezeptoraktive Carboxamid-substituierte Indolizin­-Derivate der allgemeinen Formel (I) wobei X eine Gruppe mit der allgemeinen Formel (X1) repräsentiert.

  本发明涉及具有神经受体活性的羧酰胺取代的吲哩啉衍生物，其一般式为（I），其中X代表一种具有一般式（X1）的基团。
• Indolizine Carboxamides and Aza and Diaza Derivatives Thereof
  申请人：Gmeiner Peter

  公开号：US20080051409A1

  公开（公告）日：2008-02-28

  The present invention concerns neuroreceptor-active carboxamide-substituted indolizine derivatives of general formula I wherein X represents a group of general formula X1

  本发明涉及一般式I的神经受体活性羧酰胺取代吲哚啉衍生物，其中X代表一般式X1的基团。
• Azaindole Carboxamides
  申请人：Gmeiner Peter

  公开号：US20070299091A1

  公开（公告）日：2007-12-27

  The invention relates to azaindole derivatives of general formula (I), wherein X represents a group of general formula (X1). Said compounds have a therapeutic potential in the treatment of diseases that are accompanied by an impaired dopamine metabolism and/or abnormal serotonin-5-HT1a signal transmission.

  本发明涉及通式(I)的吡唑吲衍生物，其中X代表通式（X1）的一个基团。所述化合物在治疗伴随有受损的多巴胺代谢和/或异常的5-羟色胺-1a信号传递的疾病方面具有治疗潜力。
• AZAINDOLCARBOXAMIDE
  申请人：SCHWARZ PHARMA AG

  公开号：EP1771448A1

  公开（公告）日：2007-04-11
• CARBOXAMIDE DES INDOLIZINS UND SEINER AZA- UND DIAZADERIVATE
  申请人：SCHWARZ PHARMA AG

  公开号：EP1778685B1

  公开（公告）日：2008-03-26