去甲基马普替林 | 5721-37-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 中文名称: 去甲基马普替林
• 中文别名: N,N-二乙基-2,3,3-三氟丙烯酰基酰胺
• 英文名称: Desmethylmaprotiline
• 英文别名: 3-(1-tetracyclo[6.6.2.02,7.09,14]hexadeca-2,4,6,9,11,13-hexaenyl)propan-1-amine
• CAS: 5721-37-9
• 化学式: C₁₉H₂₁N
• 分子量: 263.382
• InChiKey: IFHUOEQJTQWFGJ-UHFFFAOYSA-N

物化性质

• 碰撞截面：
  163.1 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]
• 保留指数：
  2307.2

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  1

ADMET

代谢

去甲基马普托林是马普托林的人类已知代谢物。

Desmethylmaprotiline is a known human metabolite of maprotiline.

来源:NORMAN Suspect List Exchange

反应信息

• 作为反应物：
  描述：

  去甲基马普替林 、 乙酸酐 生成 Acetamide, N-(3-(9,10-ethanoanthracen-9(10H)-yl)propyl)-
  参考文献：
  名称：

  DREBIT, ROBERT;BAKER, GLEN B.;DEWHURST, WILLIAM G., J. CHROMATOGR. BIOMED. APPL., 432,(1988) C. 334-339

  摘要：

  DOI：
• 作为产物：
  描述：

  盐酸马普替林 在 human liver microsomes 、 NADPH-generating system 作用下， 以 phosphate buffer 为溶剂， 反应 0.25h， 生成 去甲基马普替林
  参考文献：
  名称：

  Cytochrome P-450 Enzymes Contributing to Demethylation of Maprotiline in Man

  摘要：

  Abstract: From case reports of patients treated with the tetracyclic antidepressant drug maprotiline, it appears that this drug is subject to polymorphic metabolism. Thus, we studied formation of the major maprotiline metabolite desmethylmaprotiline to identify the human cytochrome P‐450 enzymes (CYP) involved. In incubations with human liver microsomes from two different donors, the substrate maprotiline was used at five different concentrations (5 to 500 μM). For selective inhibition of CYPs, quinidine (0.5–50 μM; CYP2D6), furafylline (0.3–30 μM; CYP1A2), ketoconazole (0.2–20 μM; CYP3A4), mephenytoin (20–200 μM; CYP2C19), chlorzoxazone (1–100 μM; CYP2E1), sulphaphenazole (0.2–100 μM; CYP2C9) and coumarin (0.2–100 μM; CYP2A6) were used. Desmethylmaprotiline concentrations were measured by HPLC, and enzyme kinetic parameters were estimated using extended Michaelis‐Menten equations with non‐linear regression. Relevant inhibition of the desmethylmaprotiline formation rate was observed in incubations with quinidine, furafylline and ketoconazole only. Formation rates of desmethylmaprotiline were consistent with a two enzyme model with a high (KM=71 and 84 μM) and a low (KM=531 and 426 μM) affinity site for maprotiline in the two samples, respectively. The high affinity site was competitively inhibited by quinidine (Ki,c 0.13 and 0.61 μM), the low‐affinity site was non‐competitively inhibited by furafylline (Ki,nc 0.11 and 1.3 μM). Thus it appears that CYP2D6 and CYP1A2 contribute to maprotiline demethylation. Based on the parameters obtained, for plasma concentrations of 1 μM 83% (mean) of desmethylmaprotiline formation in vivo is expected to be mediated by CYP2D6 while 17% only may be attributed to CYP1A2 activity.

  DOI：

  10.1034/j.1600-0773.2002.900306.x

文献信息

• US4017542A
  申请人：——

  公开号：US4017542A

  公开（公告）日：1977-04-12
• US4045580A
  申请人：——

  公开号：US4045580A

  公开（公告）日：1977-08-30