buprenorphine

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: buprenorphine
• 英文别名: (1S,2S,6R,14R,15R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylbutan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol
• 化学式: C₂₉H₄₁NO₄
• 分子量: 467.649
• InChiKey: RMRJXGBAOAMLHD-UGIYAZKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  buprenorphine 在 human cDNA-expressed CYP 19 glucose-6-phosphate dehydrogenase 、 D-葡萄糖-6-磷酸 、 烟酰胺腺嘌呤双核苷酸磷酸盐 作用下， 以 phosphate buffer 为溶剂， 反应 0.25h， 生成 norbuprenorphine
  参考文献：
  名称：

  Aromatase Is the Major Enzyme Metabolizing Buprenorphine in Human Placenta

  摘要：

  Buprenorphine (BUP) is a partial opiate agonist used for treatment of the adult and the pregnant addicted to this class of narcotics. The kinetic parameters for transplacental transfer and the metabolism of BUP during its perfusion in a placental lobule were the subject of an earlier report from our laboratory. The aim of this investigation is to identify and characterize the enzyme catalyzing the metabolism of BUP in term human placenta. Norbuprenorphine (norBUP) is the only metabolite formed as determined by high performance liquid chromatography and mass spectrometry. The activity of the enzyme responsible for BUP metabolism is highest in the microsomal fraction and lowest in the cytosolic, with the mitochondrial in between. Compounds with selective affinity to the enzyme aromatase (CYP 19), namely 4-hydroxyandrostenedione and aminoglutethimide, caused >70% inhibition of norBUP formation. Monoclonal antibodies raised against CYP 19 were the most potent inhibitors of BUP dealkylation. A comparison between the data obtained from the saturation isotherm for BUP dealkylation by placental microsomes and a commercially available system of cDNA-expressed CYP 19 indicated similar kinetic parameters, with apparent K m values of 12 ± 4.0 and 14 ± 8.0 μM, respectively. Therefore, aromatase is the major enzyme catalyzing the biotransformation of BUP to norBUP in term human placentas obtained from healthy pregnancies. The minor involvement of other cytochrome P450 isoforms or enzyme(s) in the metabolism of BUP in placental tissue cannot be ruled out.

  DOI：

  10.1124/jpet.103.053199

文献信息

• METHOD OF MANUFACTURING BUPRENORPHINE AND ANALOGUES THEREOF FROM ORIPAVINE
  申请人：SIEGFRIED AG

  公开号：US20170319574A1

  公开（公告）日：2017-11-09

  The invention relates to an improved method of preparing buprenorphine, a salt thereof, analogues of buprenorphine and their salts. In particular, the invention relates to a method of preparing buprenorphine and related products and salts in economic and ecologic ways having increased yields.

  本发明涉及一种改进的制备布洛芬啡、其盐、布洛芬啡类似物及其盐的方法。特别地，本发明涉及一种在经济和生态方面具有增加产量的制备布洛芬啡及相关产品和盐的方法。
• Methods for One-Pot N-Demethylation/N-Functionalization of Morphine and Tropane Alkaloids
  申请人：Hudlicky Tomas

  公开号：US20110313163A1

  公开（公告）日：2011-12-22

  The present invention provides a method for the N-demethylation and N-functionalization of an N-methylated heterocycle such as a morphine alkaloid or tropane alkaloid. The method comprises reacting the heterocycle with an functionalization agent in the presence of a transition metal catalyst in air or in the presence of an oxidant.

  本发明提供了一种用于N-去甲基化和N-官能化的方法，该方法适用于N-甲基杂环化合物，例如吗啡生物碱或曲剪生物碱。该方法包括在过渡金属催化剂的存在下，在空气中或在氧化剂的存在下，将杂环化合物与官能化试剂反应。
• METHODS FOR ONE-POT N-DEMETHYLATION/N-FUNCTIONALIZATION OF MORPHINE AND TROPANE ALKALOIDS
  申请人：Brock University

  公开号：US20150152120A1

  公开（公告）日：2015-06-04

  The present invention provides a method for the N-demethylation and N-functionalization of an N-methylated heterocycle such as a morphine alkaloid or tropane alkaloid. The method comprises reacting the heterocycle with an functionalization agent in the presence of a transition metal catalyst in air or in the presence of an oxidant.

  本发明提供了一种对N-甲基杂环，如吗啡生物碱或曲柳生物碱进行N-脱甲基化和N-官能化的方法。该方法包括在空气中或在氧化剂存在下，将杂环与官能化试剂在过渡金属催化剂的存在下反应。
• US8962841B2
  申请人：——

  公开号：US8962841B2

  公开（公告）日：2015-02-24
• US9340550B2
  申请人：——

  公开号：US9340550B2

  公开（公告）日：2016-05-17