Z-10-hydroxyamitriptyline | 1159-82-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: Z-10-hydroxyamitriptyline
• 英文别名: (Z)-N,N-dimethyl-3-(10,11-dihydro-10-hydroxy-5H-dibenzocycloheptene)-Δ^5,γ-propylamine；10-Hydroxy-amitriptylin；5-<3-Dimethylamino-propyliden>-10-hydroxy-10,11-dihydro-5H-dibenzocyclohepten；10-Hydroxyamitriptyline；2-[3-(dimethylamino)propylidene]tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaen-9-ol
• CAS: 1159-82-6
• 化学式: C₂₀H₂₃NO
• 分子量: 293.409
• InChiKey: GHWBJXOKAFHZAI-UHFFFAOYSA-N

物化性质

• 沸点：
  453.3±45.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)
• 碰撞截面：
  167.6 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  Dimethyl-{3-[10-piperidin-1-yl-dibenzo[a,d]cyclohepten-(5E)-ylidene]-propyl}-amine 在 盐酸 、 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 3.5h， 生成 Z-10-hydroxyamitriptyline
  参考文献：
  名称：

  Synthesis and NMR Studies of Z- and E-Isomers of 10-Oxo and 10-Hydroxy Derivatives of Amitriptyline and Nortriptyline.

  摘要：

  DOI：

  10.3891/acta.chem.scand.37b-0335

文献信息

• Regioselectivity and Substrate Concentration-dependency of Involvement of the CYP2D Subfamily in Oxidative Metabolism of Amitriptyline and Nortriptyline in Rat Liver Microsomes
  作者：Yasuhiro Masubuchi、Takashi Iwasa、Shoichi Fujita、Tokuji Suzuki、Toshiharu Horie、Shizuo Narimatsu

  DOI：10.1111/j.2042-7158.1996.tb06003.x

  日期：2011.4.12

  Kinetic analysis of the metabolism of amitriptyline and nortriptyline using liver microsomes from Wistar rats showed that more than one enzyme was involved in each reaction except for monophasic amitriptyline N-demethylation. The Vmax values particularly in the high-affinity sites for E-10-hydroxylation of both drugs were larger than those for Z-10-hydroxylations. Their E- and Z-10-hydroxylase activities in Dark-Agouti rats, which are deficient for CYP2D1, were significantly lower than those in Wistar rats at a lower substrate concentration (5 μM). The strain difference was reduced at a higher substrate concentration (500 μM). A similar but a smaller strain difference was also observed in nortriptyline N-demethylase activity, and a pronounced sex difference (male &gt; female) was observed in N-demethylation of both drugs in Wistar and Dark-Agouti rats. The reactions with the strain difference were inhibited concentration-dependently by sparteine, a substrate of the CYP2D subfamily, and an antibody against a CYP2D isoenzyme. The profiles of these decreased metabolic activities corresponded to that of the lower metabolic activities in Dark-Agouti rats.

  These results indicated that a cytochrome P450 isozyme in the CYP2D subfamily was involved in E- and Z- 10-hydroxylations of amitriptyline and nortriptyline in rat liver microsomes as a major isozyme in a low substrate concentration range. It seems likely that the CYP2D enzyme contributes to nortriptyline N-demethylation.

  摘要：对Wistar大鼠肝微粒体中阿米替林和诺替林代谢的动力学分析表明，除了单相阿米替林N-去甲基化反应外，每个反应中涉及多种酶。尤其是在高亲和位点上，两种药物的E-10-羟基化的Vmax值比Z-10-羟基化的要大。在缺乏CYP2D1的Dark-Agouti大鼠中，这两种药物的E-和Z-10-羟化活性在较低底物浓度（5 μM）下明显低于Wistar大鼠。在较高底物浓度（500 μM）下，品系差异减小。在诺替林N-去甲基酶活性中也观察到类似但较小的品系差异，而在Wistar和Dark-Agouti大鼠中，两种药物的N-去甲基化反应中观察到明显的性别差异（男性>女性）。具有品系差异的反应受到CYP2D亚家族底物斯帕替因和抗CYP2D同工酶抗体的浓度依赖性抑制。这些降低的代谢活性的特征与Dark-Agouti大鼠中较低的代谢活性相符。 这些结果表明，在低底物浓度范围内，CYP2D亚家族的一种细胞色素P450同工酶参与了大鼠肝微粒体中阿米替林和诺替林的E-和Z-10-羟基化作用，作为一个主要同工酶。CYP2D酶可能有助于诺替林N-去甲基化。
• Synthesis and NMR Studies of Z- and E-Isomers of 10-Oxo and 10-Hydroxy Derivatives of Amitriptyline and Nortriptyline.
  作者：Niels Lassen、Jens Perregaard、Toshiaki Nishida、Curt R. Enzell、Jan-Eric Berg、Thomas W. Dingle、Richard Vaughan Williams、Ramanathan Mahedevan

  DOI：10.3891/acta.chem.scand.37b-0335

  日期：——