N-cyclopropylmethyl-6,14-endo-ethano-7-(2-hydroxy-3,3-dimethyl)tetrahydronorthebaine | 204855-52-7

• 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: N-cyclopropylmethyl-6,14-endo-ethano-7-(2-hydroxy-3,3-dimethyl)tetrahydronorthebaine
• 英文别名: 3-O-methylbuprenorphine；2-[(1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-11,15-dimethoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-16-yl]-3,3-dimethylbutan-2-ol
• CAS: 204855-52-7
• 化学式: C₃₀H₄₃NO₄
• 分子量: 481.676
• InChiKey: TWUKPJNGRBWVGE-IOMUPEQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-cyclopropylmethyl-6,14-endo-ethano-7-(2-hydroxy-3,3-dimethyl)tetrahydronorthebaine 在 丙烷-1-硫醇 、 sodium hydride 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 3.0h， 生成 叔丁啡
  参考文献：
  名称：

  Structural Determinants of Opioid and NOP Receptor Activity in Derivatives of Buprenorphine

  摘要：

  The unique pharmacological profile of buprenorphine has led to its considerable success as an analgesic and as a treatment agent for drug abuse. Activation of nociceptin/orphanin FQ peptide (NOP) receptors has been postulated to account for certain aspects of buprenorphine's behavioral profile. In order to investigate the role of NOP activation further, a series of buprenorphine analogues has been synthesized with the aim of increasing affinity for the NOP receptor. Binding and functional assay data on these new compounds indicate that the area around C20 in the orvinols is key to NOP receptor activity, with several compounds displaying higher affinity than buprenorphine. One compound, 1b, was found to be a mu opioid receptor partial agonist of comparable efficacy to buprenorphine but with higher efficacy at NOP receptors.

  DOI：

  10.1021/jm2003238
• 作为产物：
  描述：

  溴代叔丁烷 、 7α-acetyl-17-cyclopropylmethyl-6,14-endo(ethano)tetrahydronorthebaine 在 碘 、 magnesium 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 20.0h， 生成 N-cyclopropylmethyl-6,14-endo-ethano-7-(2-hydroxy-3,3-dimethyl)tetrahydronorthebaine
  参考文献：
  名称：

  Structural Determinants of Opioid and NOP Receptor Activity in Derivatives of Buprenorphine

  摘要：

  The unique pharmacological profile of buprenorphine has led to its considerable success as an analgesic and as a treatment agent for drug abuse. Activation of nociceptin/orphanin FQ peptide (NOP) receptors has been postulated to account for certain aspects of buprenorphine's behavioral profile. In order to investigate the role of NOP activation further, a series of buprenorphine analogues has been synthesized with the aim of increasing affinity for the NOP receptor. Binding and functional assay data on these new compounds indicate that the area around C20 in the orvinols is key to NOP receptor activity, with several compounds displaying higher affinity than buprenorphine. One compound, 1b, was found to be a mu opioid receptor partial agonist of comparable efficacy to buprenorphine but with higher efficacy at NOP receptors.

  DOI：

  10.1021/jm2003238

文献信息

• Demethylation of Reticuline and Derivatives Thereof with Fungal Cytochrome P450
  申请人：River Stone Biotech APS

  公开号：US20210230655A1

  公开（公告）日：2021-07-29

  The invention relates to recombinant host cells that expresses one or more genes encoding a cytochrome P450 enzyme capable of N-demethylating and/O-demethylating reticuline and/or derivatives thereof, and also methods of producing a N-demethylated and/or O-demethylated reticuline and/or derivatives thereof, comprising cultivating the recombinant host of the invention in a culture medium under conditions in which the one or more genes encoding the cytochrome P450 enzymes is/are expressed. The reticuline and derivatives thereof are useful for providing access to naturally unavailable and chemically difficult-to-produce starting materials for opioids.

  该发明涉及重组宿主细胞，该细胞表达一个或多个编码细胞色素P450酶的基因，该酶能够对莱角碱和/或其衍生物进行N-去甲基化和/或O-去甲基化，并且还涉及生产N-去甲基化和/或O-去甲基化的莱角碱和/或其衍生物的方法，包括在培养基中培养该发明的重组宿主细胞，在该条件下，编码细胞色素P450酶的一个或多个基因被表达。莱角碱及其衍生物可用于提供自然无法获得和化学上难以生产的阿片类药物的起始物质。
• PROCESS FOR THE PREPARATION OF OPIOID COMPOUNDS
  申请人：NORAMCO, INC.

  公开号：US20150315204A1

  公开（公告）日：2015-11-05

  The present invention is directed to a process for the preparation of opioid compounds such as buprenorphine, naltrexone, naloxone, nalbuphone, nalbuphine, and the like.

  本发明涉及一种制备阿片类化合物（如布洛芬、纳曲酮、纳洛酮、纳布酮、纳布啶等）的方法。
• Acetate salt of buprenorphine and methods for preparing buprenorphine
  申请人：Rhodes Technologies

  公开号：US10278967B2

  公开（公告）日：2019-05-07

  The present disclosure provides acetate salts of buprenorphine, and its anhydrates, solvates, hydrates, and crystalline forms thereof, where the acetate salts of buprenorphine are essentially free of impurities. The disclosure further provides method of preparing the acetate salts, buprenorphine free base prepared from the acetate salts, other salts prepared from the free base, and pharmaceutical compositions thereof essentially free of impurities.

  本公开提供了丁丙诺啡的乙酸盐及其无水物、溶液、水合物和结晶形式，其中丁丙诺啡的乙酸盐基本上不含杂质。本公开进一步提供了制备乙酸盐、由乙酸盐制备的丁丙诺啡游离基、由游离基制备的其他盐及其药物组合物的方法，这些方法基本上不含杂质。
• ACETATE SALT OF BUPRENORPHINE AND METHODS FOR PREPARING BUPRENORPHINE
  申请人：Rhodes Technologies

  公开号：US20180162866A1

  公开（公告）日：2018-06-14

  The present disclosure provides acetate salts of buprenorphine, and its anhydrates, solvates, hydrates, and crystalline forms thereof, where the acetate salts of buprenorphine are essentially free of impurities. The disclosure further provides method of preparing the acetate salts, buprenorphine free base prepared from the acetate salts, other salts prepared from the free base, and pharmaceutical compositions thereof essentially free of impurities.
• PREPARATION OF BUPRENORPHINE
  申请人：VAN WILTENBURG Jimmy

  公开号：US20210380597A1

  公开（公告）日：2021-12-09

  Disclosed are methods for preparing buprenorphine from, for example, compounds such as nororipavine and northebaine.