(E)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzocycloheptene)-Δ^5,γ-propylamine | 37508-15-9

• 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: (E)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzocycloheptene)-Δ^5,γ-propylamine
• 英文别名: E-10-Oxonortriptyline；(E)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzo[a,d]cycloheptene)-Δ^5,γ-propylamine；(2E)-2-[3-(methylamino)propylidene]tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaen-9-one
• CAS: 37508-15-9
• 化学式: C₁₉H₁₉NO
• 分子量: 277.366
• InChiKey: ANQZBOSTSBYMBP-LFIBNONCSA-N

物化性质

• 沸点：
  455.2±44.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzocycloheptene)-Δ^5,γ-propylamine 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.5h， 生成 反式-10-羟基去甲替林
  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
• 作为产物：
  描述：

  Dimethyl-{3-[10-piperidin-1-yl-dibenzo[a,d]cyclohepten-(5E)-ylidene]-propyl}-amine 在 盐酸 、 potassium dihydrogenphosphate 、 锌 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 7.0h， 生成 (E)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzocycloheptene)-Δ^5,γ-propylamine
  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

• Stereoselective reversible ketone formation from 10-hydroxylated nortriptyline metabolites in human liver
  作者：U. Breyer-Pfaff、K. Nill

  DOI：10.3109/00498259509061920

  日期：1995.1

  1. E- and Z-10-hydroxynortriptyline are major metabolites of amitriptyline and nortriptyline in man. Upon incubation with human liver microsomes or cytosol, these metabolites were oxidized to the corresponding ketones, E- and Z-10-oxonortriptyline. (+)-E- and (+)-Z-10-hydroxynortriptyline were distinctly preferred over the (-)-isomers as substrates. NADP(+) supported the oxidation in cytosol whereas in microsomes NAD(+) was the best cofactor.2. Incubation of E- and Z-10-oxonortriptyline with NADPH and cytosol resulted in the nearly exclusive formation of (+)-E- and (+)-Z-10-hydroxynortriptyline. Kinetic analysis revealed high-affinity reduction (K-m 1-2 mu M) of the two ketones and an additional low-affinity component with the E-isomer. 10-Oxonortriptyline reduction was also catalysed by rabbit, but not by rat or guinea pig liver cytosol.3. With [4-H-3]NADPH as cosubstrate, tritium was incorporated into E- and Z-10-hydroxynortriptyline preferentially from the pro-4R position. Redox cycling of (+)-E- and (+)-Z-10-hydroxynortriptyline in cytosol in the presence of NAD(+) and NADPH was indicated by H-3 incorporation from [pro-4R-H-3]NADPH.4. Recombinant human carbonyl reductase catalysed low-affinity reduction of E-10-oxonortriptyline with preferential transfer of the pro-4S-H-3 of labelled NADPH.5. Ketone reduction in cytosol was strongly inhibited by 9,10-phenanthrenequinone and dehydrolithocholic acid and moderately by other 3-oxo steroids and some antiinflammatory drugs.6. The high-affinity reduction of E- and Z-10-oxonortriptyline and the oxidation of the alcohols in cytosol are probably mediated by a member of the aldo-keto reductase family of enzymes.