莫氯贝胺N-氧化物 | 64544-24-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 莫氯贝胺N-氧化物
• 中文别名: 莫氯贝胺N-氧化物
• 英文名称: Ro 12-5637
• 英文别名: moclobemide-N-oxide；Benzamide, 4-chloro-N-(2-(4-morpholinyl)ethyl)-, N-oxide；4-chloro-N-[2-(4-oxidomorpholin-4-ium-4-yl)ethyl]benzamide
• CAS: 64544-24-7
• 化学式: C₁₃H₁₇ClN₂O₃
• 分子量: 284.743
• InChiKey: CJTZZADPEGGIMM-UHFFFAOYSA-N

物化性质

• 溶解度：
  少许溶于甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  -20°C储存

制备方法与用途

吗氯贝胺N-氧化物（Ro 12-5637）是吗氯贝胺的N-氧化物代谢产物。尽管它保留了一定程度的MAO-A抑制活性，但通常以较低浓度存在。吗氯贝胺N-氧化物可以通过在240 nm处检测其紫外吸收来识别。

反应信息

• 作为产物：
  描述：

  吗氯贝胺 在 human flavin monooxygenase-3 recombinant 、 β-烟酰胺腺嘌呤二核苷酸 、 sodium citrate 、 magnesium chloride 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以55%的产率得到莫氯贝胺N-氧化物
  参考文献：
  名称：

  Expression of recombinant human flavin monooxygenase and moclobemide-N-oxide synthesis on multi-mg scale

  摘要：

  在大肠杆菌中异源表达了一系列人类黄素单加氧酶，从而获得了用于体外制备人类药物代谢物的即用型生物催化剂。甲氧苄啶-N-氧化物（65 毫克）是第一个用重组 hFMO3 制备的多毫克级高价代谢物。

  DOI：

  10.1039/c2cc17878h

文献信息

• Methods and compositions for using moclobemide
  申请人：——

  公开号：US20020032197A1

  公开（公告）日：2002-03-14

  The invention relates to methods and compositions for treating, managing, and/or preventing certain pain and pain disorder, posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder and premenstrual syndrome, certain sleep disorders, eating disorders, and symptoms thereof using moclobemide, a moclobemide metabolite, a moclobemide derivative or a moclobemide composition.

  本发明涉及使用吗氯贝胺、吗氯贝胺代谢物、吗氯贝胺衍生物或吗氯贝胺组合物治疗、控制和/或预防某些疼痛和疼痛障碍、创伤后应激障碍（PTSD）、经前期精神障碍和经前期综合征、某些睡眠障碍、进食障碍及其症状的方法和组合物。
• Characterization of moclobemide<i>N</i>-oxidation in human liver microsomes
  作者：J. Hoskins、G. Shenfield、M. Murray、A. Gross

  DOI：10.1080/00498250110055488

  日期：2001.1

  1. Moclobemide undergoes morpholine ring N-oxidation to form a major metabolite in plasma, Ro12-5637.2. The kinetics of moclobemide N-oxidation in human liver microsomes (HLM). (n = 6) have been investigated and the mixed-function oxidase enzymes catalysing this reaction have been identified using inhibition, enzyme correlation, altered pH and heat pretreatment experiments.3. N-oxidation followed single enzyme Michealis-Menten kinetics (0.02-4.0 mM). K-m (app) and V-max ranged from 0.48 to 1.35 mM (mean +/- SD 0.77 +/- 0.34 mM) and 0.22 to 2.15 nmol mg(-1) min(-1) (1.39 +/- 0.80 nmol mg(-1) min(-1)), respectively.4. The N-oxidation of moclobemide strongly correlated with benzydamine N-oxidation, a probe reaction for flavin-containing monooxygenase (FMO) activity, (0.1 mM moclobemide, r(S) = 0.81; p < 0.005; 4 mM moclobemide, r(S) = 0.94; p = 0.0001). Correlations were observed between moclobemide N-oxidation and specific cytochrome P450 (CYP) activities at both moclobemide concentrations (0.1 mM moclobemide, CYP2C19 r(S) = 0.66; p < 0.05; 4 mM moclobemide, CYP2E1 r(S) = 0.56; p < 0.05).5. The general P450 inhibitor, N-benzylimidazole, did not affect the rate of Ro12-5637 formation (0% inhibition versus control) at 1.3 mM moclobemide. Furthermore, the rate of Ro12-5637 formation in HLM was unaffected by inhibitors or substrates of specific P450s (< 10% inhibition versus control).6. Heat pretreatment of HLM in the absence of NADPH (inactivating FMOs) resulted in 97% inhibition of Ro12-5637 formation. N-oxidation activity was greatest when incubated at pH 8.5. These results are consistent with the reaction being FMO mediated.7. In conclusion, moclobemide N-oxidation activity has been observed in HLM in vitro and the reaction is predominantly catalysed by FMOs with a potentially small contribution from cytochrome P450 isoforms.
• NAKAI, S.;KOBAYASHI, T.;EZAWA, T., J. CHROMATOGR., 479,(1989) N, C. 459-463
  作者：NAKAI, S.、KOBAYASHI, T.、EZAWA, T.

  DOI：——

  日期：——
• [EN] METHODS AND COMPOSITIONS FOR USING MOCLOBEMIDE<br/>[FR] PROCEDES ET COMPOSITIONS D'UTILISATION DE MOCLOBEMIDE
  申请人：JANUS PHARMACEUTICALS INC

  公开号：WO2000006138A2

  公开（公告）日：2000-02-10

  The invention relates to methods and compositions for treating, managing, and/or preventing certain pain and pain disorder, posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder and premenstrual syndrome, certain sleep disorders, eating disorders, and symptoms thereof using moclobemide, a moclobemide metabolite, a moclobemide derivative or a moclobemide composition.