(Z)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzocycloheptene)-Δ^5,γ-propylamine | 37440-22-5

• 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)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzocycloheptene)-Δ^5,γ-propylamine
• 英文别名: Z-10-Oxonortriptyline；Z-10-oxo nortriptyline；(Z)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzo[a,d]cycloheptene)-Δ^5,γ-propylamine；(2Z)-2-[3-(methylamino)propylidene]tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,11,13-hexaen-9-one
• CAS: 37440-22-5
• 化学式: C₁₉H₁₉NO
• 分子量: 277.366
• InChiKey: ANQZBOSTSBYMBP-WJDWOHSUSA-N

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：

  (Z)-N-methyl-3-(10,11-dihydro-10-oxo-5H-dibenzocycloheptene)-Δ^5,γ-propylamine 在 human aldo-keto reductase AKR₁C₁ 、 还原型辅酶II(NADPH)四钠盐 作用下， 反应 0.07h， 生成 顺式-10-羟基去甲替林
  参考文献：
  名称：

  通过人肝脏的醛酮还原酶高选择性地选择性还原酮替芬和酮基去甲替林代谢物的对映异构体。

  摘要：

  醛基酮还原酶（AKR）形成酶超家族，催化羰基化合物的还原，在某些情况下还催化醇的逆氧化。特别是，AKR1C家族已考虑在药物代谢中发挥作用，但已发表的数据未能揭示低Km药物底物。此外，尚未建立使用化学相关底物的结构活性关系。在本研究中，开发了一种改良的方法，用于从人肝细胞质液中分离出AKR1C1、1C2和1C4（二氢二醇脱氢酶1、2和4）以及羰基还原酶（EC 1.1.1.184）。链醇脱氢酶超家族。使用结构相似的底物（R）-和（S）-酮替芬以及E-和Z-10-氧杂三联蛋白研究了紧密相关的酶AKR1C1和1C2对NADPH依赖性还原的动力学。Km值在2.6和53 microM之间变化，Vmax在5和313 mU / mg蛋白之间变化；用AKR1C1还原E-和Z-10-氧杂三联碱可在30 microM左右的Ki抑制底物。该反应是严格立体定向的，从每种酮替芬对映体产生一种对映醇，以及E-和Z-10

  DOI：

  10.1016/s0006-2952(99)00319-6
• 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 (Z)-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.
• High-affinity stereoselective reduction of the enantiomers of ketotifen and of ketonic nortriptyline metabolites by aldo–keto reductases from human liver
  作者：Ursula Breyer-Pfaff、Karl Nill

  DOI：10.1016/s0006-2952(99)00319-6

  日期：2000.2

  investigation, a modified procedure was developed for the isolation of AKR1C1, 1C2, and 1C4 (dihydrodiol dehydrogenases 1, 2, and 4) from human liver cytosol along with carbonyl reductase (EC 1.1.1.184), a member of the short-chain alcohol dehydrogenase superfamily. The kinetics of NADPH-dependent reduction by the closely related enzymes AKR1C1 and 1C2 were studied with the structurally similar substrates

  醛基酮还原酶（AKR）形成酶超家族，催化羰基化合物的还原，在某些情况下还催化醇的逆氧化。特别是，AKR1C家族已考虑在药物代谢中发挥作用，但已发表的数据未能揭示低Km药物底物。此外，尚未建立使用化学相关底物的结构活性关系。在本研究中，开发了一种改良的方法，用于从人肝细胞质液中分离出AKR1C1、1C2和1C4（二氢二醇脱氢酶1、2和4）以及羰基还原酶（EC 1.1.1.184）。链醇脱氢酶超家族。使用结构相似的底物（R）-和（S）-酮替芬以及E-和Z-10-氧杂三联蛋白研究了紧密相关的酶AKR1C1和1C2对NADPH依赖性还原的动力学。Km值在2.6和53 microM之间变化，Vmax在5和313 mU / mg蛋白之间变化；用AKR1C1还原E-和Z-10-氧杂三联碱可在30 microM左右的Ki抑制底物。该反应是严格立体定向的，从每种酮替芬对映体产生一种对映醇，以及E-和Z-10
• 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：——