Erythrohydrobupropion | 99102-04-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Erythrohydrobupropion
• 英文别名: threo-hydrobupropion；(+/-)-(erythro)-2-tert-butylamino-1-(3-chlorophenyl)propan-1-ol；(1S,2R)-2-(tert-butylamino)-1-(3-chlorophenyl)propan-1-ol
• CAS: 99102-04-2
• 化学式: C₁₃H₂₀ClNO
• 分子量: 241.761
• InChiKey: NDPTTXIBLSWNSF-BXKDBHETSA-N

物化性质

• 熔点：
  51-52°C
• 沸点：
  347.2±27.0 °C(Predicted)
• 密度：
  1.078
• 溶解度：
  溶于氯仿、DMSO、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Erythrohydrobupropion 在 P₄₅₀ CYP₂C₁₉ enzyme 、 还原型辅酶Ⅰ 作用下， 以 aq. phosphate buffer 为溶剂， 反应 0.42h， 生成 4'-hydroxyerythrohydrobupropion
  参考文献：
  名称：

  人体中三种新的安非他酮代谢物的鉴定和结构表征

  摘要：

  安非他酮是一种广泛使用的抗抑郁药和推荐的CYP2B6探针药物。但是，目前对安非他酮消除途径的理解是有限的。安非他酮具有三种活性循环代谢物，OH-安非他酮，苏氢安非他酮和赤氢安非他酮，但与这些安非他酮一起，这些代谢物及其在尿液中的结合物仅占剂量的23％，并且大多数安非他酮消除途径导致未表征的代谢物。这项研究的目的是使用人类临床样品和体外孵育来确定未表征的安非他酮代谢物的结构。在人肝微粒体温育中检测到三种新的代谢物4'-OH-安非他酮，赤型4'-OH-氢安非他酮和threo-4'-OH-氢安非他酮，并从人尿液中分离出来。通过将紫外线吸收率，NMR光谱和质谱数据与合成标准样品进行比较，确认了代谢物的结构。这些代谢物合计占尿中排泄的药物相关物质的24％。

  DOI：

  10.1021/acsmedchemlett.6b00189
• 作为产物：
  描述：

  3'-氯丙酮苯 在 sodium tetrahydroborate 、 溴 作用下， 以 乙醇 为溶剂， 生成 Erythrohydrobupropion
  参考文献：
  名称：

  Synthesis and evaluation of the anticonvulsant activity of a series of 2-amino-1-phenyl-1-propanols derived from the metabolites of the antidepressant bupropion

  摘要：

  A series of 2-amino-1-phenyl-1-propanols that are structurally related to known metabolites of bupropion,1 (Wellbutrin(R)) were synthesized and evaluated as potential anticonvulsants. The (R*,R*)-2-tert-butylamino-1-(3-trifluoromethylphenyl) propanol 20 had an ED(50) of 16.5 +/- 2.8 mg/kg ip in mice in the maximal electroshock screen and was chosen for further evaluation. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00577-x

文献信息

• Metabolism of Bupropion by Carbonyl Reductases in Liver and Intestine
  作者：Jamie N. Connarn、Xinyuan Zhang、Andrew Babiskin、Duxin Sun

  DOI：10.1124/dmd.115.063107

  日期：2015.7

  Bupropion’s metabolism and the formation of hydroxybupropion in the liver by cytochrome P450 2B6 (CYP2B6) has been extensively studied; however, the metabolism and formation of erythro/threohydrobupropion in the liver and intestine by carbonyl reductases (CR) has not been well characterized. The purpose of this investigation was to compare the relative contribution of the two metabolism pathways of bupropion (by CYP2B6 and CR) in the subcellular fractions of liver and intestine and to identify the CRs responsible for erythro/threohydrobupropion formation in the liver and the intestine. The results showed that the liver microsome generated the highest amount of hydroxybupropion ( V max = 131 pmol/min per milligram, K m = 87 μ M). In addition, liver microsome and S9 fractions formed similar levels of threohydrobupropion by CR ( V max = 98–99 pmol/min per milligram and K m = 186–265 μ M). Interestingly, the liver has similar capability to form hydroxybupropion (by CYP2B6) and threohydrobupropion (by CR). In contrast, none of the intestinal fractions generate hydroxybupropion, suggesting that the intestine does not have CYP2B6 available for metabolism of bupropion. However, intestinal S9 fraction formed threohydrobupropion to the extent of 25% of the amount of threohydrobupropion formed by liver S9 fraction. Enzyme inhibition and Western blots identified that 11 β -dehydrogenase isozyme 1 in the liver microsome fraction is mainly responsible for the formation of threohydrobupropion, and in the intestine AKR7 may be responsible for the same metabolite formation. These quantitative comparisons of bupropion metabolism by CR in the liver and intestine may provide new insight into its efficacy and side effects with respect to these metabolites.

  细胞色素 P450 2B6 (CYP2B6)对安非他酮在肝脏中的代谢和羟基安非他酮的形成进行了广泛的研究；然而，羰基还原酶 (CR) 对红曲/三氢安非他酮在肝脏和肠道中的代谢和形成还没有很好的描述。这项研究的目的是比较安非他酮在肝脏和肠道亚细胞组分中两种代谢途径（CYP2B6 和 CR）的相对贡献，并确定在肝脏和肠道中形成红代/三氢安非他酮的 CR。结果表明，肝微粒体产生的羟基安非他明量最高（V max = 131 pmol/min per milligram，K m = 87 μ M）。此外，肝脏微粒体和 S9 馏分通过 CR 生成了类似水平的曲安奈德（V max = 98-99 pmol/min per milligram，K m = 186-265 μ M）。有趣的是，肝脏形成羟基安非他明（通过 CYP2B6）和曲氢安非他明（通过 CR）的能力相似。与此相反，肠道馏分均不产生羟基安非他酮，这表明肠道中没有可用于安非他酮代谢的 CYP2B6。然而，肠道 S9 组份形成的安非他酮为肝脏 S9 组份形成的安非他酮的 25%。通过酶抑制和 Western 印迹发现，肝脏微粒体部分中的 11 β - 脱氢酶同工酶 1 主要负责形成曲安奈德，而肠道中的 AKR7 可能负责形成相同的代谢物。通过这些定量比较 CR 在肝脏和肠道中的安非他酮代谢情况，可以为了解安非他酮在这些代谢物方面的疗效和副作用提供新的视角。
• [EN] BUPROPION METABOLITES AND METHODS OF THEIR SYNTHESIS AND USE<br/>[FR] METABOLITES DU BUPROPION ET LEURS PROCEDES DE SYNTHESE ET D'UTILISATION
  申请人：SEPRACOR INC

  公开号：WO2001062257A2

  公开（公告）日：2001-08-30

  Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, sexual dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. Methods of making optically pure bupropion metabolites are also disclosed.

  本发明公开了利用丁丙腈代谢物治疗神经元单胺再摄取抑制改善的疾病的方法和组合物。这些疾病包括但不限于性功能障碍、情感障碍、脑功能障碍、吸烟和失禁。本发明还公开了制备光学纯丁丙腈代谢物的方法。
• Bupropion metabolites and methods of their synthesis and use
  申请人：SEPRACOR INC.

  公开号：US20020052341A1

  公开（公告）日：2002-05-02

  Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, sexual dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. Methods of making optically pure bupropion metabolites are also disclosed.

  本文披露了利用伯泊隆代谢物治疗神经元单胺重摄取抑制所改善的疾病的方法和组合物。这些疾病包括但不限于性功能障碍、情感障碍、脑功能障碍、吸烟和失禁。本文还披露了制备光学纯伯泊隆代谢物的方法。
• Intermediates of bupropion metabolites synthesis
  申请人：Fang Qun Kevin

  公开号：US20060058300A1

  公开（公告）日：2006-03-16

  Methods and compositions are disclosed which utilize metabolites of bupropion for treating disorders ameliorated by inhibition of neuronal monoamine reuptake. Such disorders include, but are not limited to, sexual dysfunction, affective disorders, cerebral function disorders, cigarette smoking, and incontinence. Methods of making optically pure bupropion metabolites are also disclosed.

  本文公开了利用伯泊隆代谢产物治疗通过抑制神经元单胺再摄取改善的疾病的方法和组合物。这些疾病包括但不限于性功能障碍，情感障碍，脑功能障碍，吸烟和失禁。本文还公开了制备光学纯伯泊隆代谢产物的方法。
• Use of Bupropion Metabolites for the Treatment of Inflammatory Disorders
  申请人：Brew John

  公开号：US20090318562A1

  公开（公告）日：2009-12-24

  Compounds that may be used for the treatment or prevention of a condition associated with T-cell proliferation or that is mediated by pro-inflammatory cytokines are of formula (1) or a salt thereof.

  可能用于治疗或预防与T细胞增殖有关或由促炎症细胞因子介导的疾病的化合物为公式（1）或其盐。