Zotepine S-oxide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 英文名称: Zotepine S-oxide
• 英文别名: (E)-2-(8-chlorodibenzo[b,f]thiepin-10-yloxy)-N,N-dimethylethanamine 5-oxide；2-(3-chloro-11-oxobenzo[b][1]benzothiepin-5-yl)oxy-N,N-dimethylethanamine
• 化学式: C₁₈H₁₈ClNO₂S
• 分子量: 347.865
• InChiKey: GPQLECKPRFIPAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  57.8
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

佐替平-氧化物是佐替平的人类已知代谢物。

Zotepine -oxide is a known human metabolite of zotepine.

来源:NORMAN Suspect List Exchange

反应信息

• 作为产物：
  描述：

  佐替平 在 四氧化锇 、 间氯过氧苯甲酸 作用下， 以 氯仿 、 水 、 叔丁醇 为溶剂， 反应 19.68h， 生成 Zotepine S-oxide
  参考文献：
  名称：

  常用抗精神病药的1相苯氮平N-氧化物的合成及氧化性能

  摘要：

  摘要 越来越多的证据表明，广泛使用的抗精神病药会氧化细胞成分，但直到现在，基本化学仍不清楚。众所周知，这类药物容易经历N-氧化作为第一步关键的代谢步骤。为了深入了解问题，第三阶段1个ñ -oxides氯氮平，奥氮平，喹硫平，和佐替平，合成，与一起Ñ，小号-dioxides喹硫平与佐替平的。这些N然后对氧化物进行完善的化学转化，以测试其在第VIII族过渡金属催化的反应中的氧化性能。在四氧化催化的苯乙烯或肉桂醇的二羟基化反应中以及在四丙基过钌酸催化的肉桂醇的氧化反应中，苯并pine庚因N-氧化物可以替代标准氧化剂N-甲基吗啉N-氧化物（NMO）效率。从化学角度看，氯氮平N氧化物显示出可与NMO媲美的氧化能力，表明苯并ze以氧为载体。此外，发现喹硫平是优良的双氧受体，经历了最初的N-氧化和随后的S-氧化。因此，值得考虑的是，对人体的氧化损伤是否可能与普通抗精神病药的潜在氧化还原特性有关。 越来越

  DOI：

  10.1055/s-0033-1338519

文献信息

• [EN] 11-OXO-10,11-DIHYDRODIBENZO[B,F][1,4]THIAZEPINE S-OXIDE DERIVATIVES AND THEIR USE AS DOPAMINE D2 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE 11-OXO-10,11-DIHYDRODIBENZO[B,F][1,4]THIAZÉPINE S-OXYDE ET LEUR UTILISATION COMME ANTAGONISTES DU RÉCEPTEUR D2 DE LA DOPAMINE
  申请人：US HEALTH

  公开号：WO2015017412A1

  公开（公告）日：2015-02-05

  The disclosure includes compounds and pharmaceutically acceptable salts of Formula (I). Certain compounds and salts of Formula (I) are selective inhibitors of the Dopamine D2 receptor. The variables R1-R4, n, and L are defined herein. The disclosure also provides methods of synthesizing compounds of Formula (I) and pharmaceutical compositions containing compounds of Formula (I). Additionally the disclosure provides methods or treating patients suffering from central nervous system disorders, including Tourette's syndrome, bipolar disorder, hyperprolactinemia, tardive dyskinesia, Huntington's chorea, psychosis, depression, or schizophrenia.

  该披露包括公式（I）的化合物和药用盐。公式（I）的某些化合物和盐是多巴胺D2受体的选择性抑制剂。变量R1-R4、n和L在此有定义。该披露还提供了合成公式（I）化合物的方法和含有公式（I）化合物的药物组合物。此外，该披露提供了治疗患有中枢神经系统疾病的患者的方法，包括抽动症、躁郁症、高泌乳素血症、迟发性运动障碍、亨廷顿舞蹈症、精神病、抑郁症或精神分裂症。
• 11-OXO-10,11-DIHYDRODIBENZO[B,F][1,4]THIAZEPINE S-OXIDE DERIVATIVES AND THEIR USE AS DOPAMINE D2 RECEPTOR ANTAGONISTS
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN

  公开号：US20160176831A1

  公开（公告）日：2016-06-23

  The disclosure includes compounds and pharmaceutically acceptable salts of Formula (I). Certain compounds and salts of Formula (I) are selective inhibitors of the Dopamine D 2 receptor. The variables R 1 -R 4 , n, and L are defined herein. The disclosure also provides methods of synthesizing compounds of Formula (I) and pharmaceutical compositions containing compounds of Formula (I). Additionally the disclosure provides methods or treating patients suffering from central nervous system disorders, including Tourette's syndrome, bipolar disorder, hyperprolactinemia, tardive dyskinesia, Huntington's chorea, psychosis, depression, or schizophrenia.

  本公开涵盖公式（I）的化合物和药物可接受的盐。公式（I）的某些化合物和盐是多巴胺D2受体的选择性抑制剂。变量R1-R4，n和L在此定义。本公开还提供了合成公式（I）化合物和含有公式（I）化合物的制药组合物的方法。此外，本公开还提供了治疗患有中枢神经系统疾病的患者的方法，包括抽动症、躁郁症、高催乳素血症、迟发性运动障碍、亨廷顿舞蹈病、精神病、抑郁症或精神分裂症。
• Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, an antipsychotic drug, in human liver microsomes
  作者：T. SHIRAGA、H. KANEKO、K. IWASAKI、Z. TOZUKA、A. SUZUKI、T. HATA

  DOI：10.1080/004982599238623

  日期：1999.1

  1. Studies using human liver microsomes and recombinant human cytochrome P450 (P450) enzymes and flavin-containing monooxygenase (FMO) were performed to identify the enzymes responsible for the formation of zotepine metabolites in man.2. Human liver microsomes produced four metabolites and a tentative order of importance was: norzotepine, 3-hydroxyzotepine, zotepine S-oxide and 2-hydroxyzotepine. Zotepine N-oxide was also detected, but it could not bt quantified.3. The rates of formation of the major metabolite, norzotepine, and zotepine S-oxide (at a substrate concentration of 20 mu M) were significantly correlated with the testosterone 6 beta-hydroxylase activities and CYP3A4 contents of the 12 different human liver microsomal samples. Inhibition studies with P450 enzyme selective inhibitors and anti-rat CYP3A2 antibodies also indicated a predominant role of CYP3A4 in the formation of norzotepine and zotepine S-oxide. Furafylline and sulphaphenazole inhibited the N-demethylation of zotepine by up to similar to 30%.4. Correlation and inhibition data for the 2- and 3-hydroxylation of zotepine were consistent with the predominant role of CYP1A2 and 2D6 in the formation of these metabolites, respectively.5. Recombinant CYP1A1, 1A2, 2B6, 2C19, 3A4 and 3A5 efficiently catalysed N-demethylation of zotepine. CYP1A1, 1A2, 2B6 and 3A4 were also active for S-oxidation. CYP1A2 and 2D6*1-Val374 efficiently produced 2-hydroxyzotepine and 3-hyroxyzotepine, respectively. Recombinant human FMO3 did not catalyse zotepine S-oxidation.6. These results suggest that both the N-demethylation and S-oxidation of zotepine are mediated mainly by CYP3A4, and that CYP1A2 and 2D6 play an important role in the 2- and 3-hydroxylation of zotepine, respectively.
• MATSUO, MASAAKI;NODA, KOSEH;VATANABEH, TAKAO
  作者：MATSUO, MASAAKI、NODA, KOSEH、VATANABEH, TAKAO

  DOI：——

  日期：——
• JPS568379A
  申请人：——

  公开号：JPS568379A

  公开（公告）日：1981-01-28