2-[4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethyl 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate | 503537-32-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 2-[4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethyl 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 503537-32-4
• 化学式: C₃₁H₄₁F₃N₄O₄S
• 分子量: 622.752
• InChiKey: MLRNILVFPIGGKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  99.6
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-[4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethyl 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以75%的产率得到Fluphenazine 4-aminobutyrate trihydrochloride
  参考文献：
  名称：

  A Mutual Prodrug Ester of GABA and Perphenazine Exhibits Antischizophrenic Efficacy with Diminished Extrapyramidal Effects

  摘要：

  The perphenazine and fluphenazine GABA esters 3 and 4 evaluated in rat models for antipsychotic activity displayed a significant decrease of catalepsy associated with increased prolactin blood levels. Efficacy was evaluated in the D-amphetamine-induced hyperactivity model, where perphenazine abolished hyperactivity and induced sedation and catalepsy, whereas 3 reduced hyperactivity without sedation or catalepsy. Thus, 3 (BL-1020) constitutes a prototype of novel antipsychotics possessing GABAergic activity. A phase II study is in progress.

  DOI：

  10.1021/jm7012453
• 作为产物：
  描述：

  N-BOC-GAMMA-氨基丁酸 、 氟奋乃静 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到2-[4-[3-[2-(Trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethyl 4-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
  参考文献：
  名称：

  A Mutual Prodrug Ester of GABA and Perphenazine Exhibits Antischizophrenic Efficacy with Diminished Extrapyramidal Effects

  摘要：

  The perphenazine and fluphenazine GABA esters 3 and 4 evaluated in rat models for antipsychotic activity displayed a significant decrease of catalepsy associated with increased prolactin blood levels. Efficacy was evaluated in the D-amphetamine-induced hyperactivity model, where perphenazine abolished hyperactivity and induced sedation and catalepsy, whereas 3 reduced hyperactivity without sedation or catalepsy. Thus, 3 (BL-1020) constitutes a prototype of novel antipsychotics possessing GABAergic activity. A phase II study is in progress.

  DOI：

  10.1021/jm7012453

文献信息

• Conjugated psychotropic drugs and uses thereof
  申请人：——

  公开号：US20040242570A1

  公开（公告）日：2004-12-02

  Novel chemical conjugates of psychotropic drugs and organic acids, uses thereof in the treatment of psychotic and/or proliferative disorders and diseases and as chemosensitizing agents, and their syntheses are disclosed. The organic acids are selected to reduce side effects induced by the psychotropic drugs and/or to exert an anti-proliferative activity.

  本发明揭示了精神药物和有机酸的新型化学结合物，其在治疗精神病和/或增生性疾病和疾病以及作为化学增敏剂中的应用，所述的有机酸被选择用于减少由精神药物引起的副作用和/或发挥抗增殖活性。同时，本发明还揭示了这些化合物的合成方法。
• CONJUGATED PSYCHOTROPIC DRUGS AND USES THEREOF
  申请人：Nudelman Abraham

  公开号：US20120309748A1

  公开（公告）日：2012-12-06

  Novel chemical conjugates of psychotropic drugs and organic acids, uses thereof in the treatment of psychotic and/or proliferative disorders and diseases and as chemosensitizing agents, and their syntheses are disclosed. The organic acids are selected to reduce side effects induced by the psychotropic drugs and/or to exert an anti-proliferative activity.

  本发明揭示了精神药物和有机酸的新型化学结合物，其用途包括治疗精神病和/或增生性疾病，作为化疗增敏剂，并且还揭示了它们的合成方法。所选有机酸被选择为减少精神药物引起的副作用和/或发挥抗增殖活性。
• Conjugated anti-psychotic drugs and uses thereof
  申请人：Ramot at Tel Aviv University Ltd.

  公开号：EP2275143A2

  公开（公告）日：2011-01-19

  A chemical conjugate comprises a first chemical moiety covalently linked to a second chemical moiety, wherein said first chemical moiety is a residue of an anti-psychotic drug residue and further wherein said second chemical moiety is a residue of an organic acid residue having 3-5 carbon atoms, said organic acid residue is selected so as to reduce side effects induced by said anti-psychotic drug when said anti-psychotic drug is administered per se and/or to exert antiproliferative activity.

  一种化学共轭物包括与第二化学分子共价连接的第一化学分子，其中所述第一化学分子是抗精神病药物残留物的残基，进一步地，其中所述第二化学分子是具有 3-5 个碳原子的有机酸残留物的残基，选择所述有机酸残留物是为了在服用所述抗精神病药物本身时减少所述抗精神病药物引起的副作用和/或发挥抗增殖活性。
• CONJUGATE OF PERPHENAZINE AND GABA AND USES THEREOF
  申请人：Ramot at Tel Aviv University Ltd.

  公开号：EP1429844B1

  公开（公告）日：2012-01-18
• CONJUGATED ANTI-PSYCHOTIC DRUGS AND USES THEREOF
  申请人：Ramot at Tel Aviv University Ltd.

  公开号：EP1429844A2

  公开（公告）日：2004-06-23