(4R,4aS,7S,7aR,12bS)-7-(benzylamino)-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol | 1257541-93-7

• 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: (4R,4aS,7S,7aR,12bS)-7-(benzylamino)-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
• CAS: 1257541-93-7
• 化学式: C₂₄H₂₈N₂O₃
• 分子量: 392.498
• InChiKey: BJWLJXOUNGKLBS-YBAXTEPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7S,7aR,12bS)-7-(benzylamino)-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol 在 盐酸 、 5% Pd/C 、 氢气 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 60.0 ℃ 、275.8 kPa 条件下， 反应 80.0h， 生成 2-[2-[[(4R,4aS,7S,7aR,12bS)-4a,9-dihydroxy-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]amino]-2-oxoethoxy]-N-[5-[[2-[2-[[(1S,2S,13R,21R)-22-(cyclopropylmethyl)-2-hydroxy-16-(2-phenylethoxy)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5(10),6,8,15,17,19(25)-heptaen-9-yl]amino]-2-oxoethoxy]acetyl]amino]pentyl]acetamide;hydrochloride
  参考文献：
  名称：

  Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers

  摘要：

  Opioid receptors, including the mu- and delta-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.

  DOI：

  10.1021/ml300083p
• 作为产物：
  描述：

  4,5alpha-环氧-3,14-二羟基-17-甲基吗喃-6-酮盐酸盐 在 sodium tetrahydroborate 、 sodium carbonate 、 对甲苯磺酸 作用下， 以 乙醇 、 水 、 苯 为溶剂， 反应 14.0h， 生成 (4R,4aS,7S,7aR,12bS)-7-(benzylamino)-3-methyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
  参考文献：
  名称：

  Tuned-Affinity Bivalent Ligands for the Characterization of Opioid Receptor Heteromers

  摘要：

  Opioid receptors, including the mu- and delta-opioid receptors (MOR and DOR), are important targets for the treatment of pain. Although there is mounting evidence that these receptors form heteromers, the functional role of the MOR/DOR heteromer remains unresolved. We have designed and synthesized bivalent ligands as tools to elucidate the functional role of the MOR/DOR heteromer. Our ligands (L2 and L4) are comprised of a compound with low affinity at the DOR tethered to a compound with high affinity at the MOR, with the goal of producing ligands with "tuned affinity" at MOR/DOR heteromers as compared to DOR homomers. Here, we show that both L2 and L4 demonstrate enhanced affinity at MOR/DOR heteromers as compared to DOR homomers, thereby providing unique pharmacological tools to dissect the role of the MOR/DOR heteromer in pain.

  DOI：

  10.1021/ml300083p

文献信息

• Preparation of 6-Alpha-Amino N-Substituted Morphinans by Catalytic Hydrogen Transfer
  申请人：Grote Christopher W.

  公开号：US20100317683A1

  公开（公告）日：2010-12-16

  The present invention provides processes for the stereoselective synthesis of 6-alpha-amino N-substituted morphinans. In particular, the invention provides processes for the reductive amination of 6-keto N-substituted morphinans by catalytic hydrogen transfer.

  本发明提供了用于立体选择性合成6-α-氨基N-取代吗啡酮类化合物的方法。具体来说，该发明提供了通过催化氢转移的还原胺化反应合成6-酮N-取代吗啡酮类化合物的方法。
• [EN] PREPARATION OF 6-ALPHA-AMINO N-SUBSTITUTED MORPHINANS BY CATALYTIC HYDROGEN TRANSFER<br/>[FR] PRÉPARATION DE MORPHINANES 6-ALPHA-AMINO N-SUBSTITUÉS PAR TRANSFERT CATALYTIQUE D'HYDROGÈNE
  申请人：MALLINCKRODT INC

  公开号：WO2010144641A1

  公开（公告）日：2010-12-16

  The present invention provides processes for the stereoselective synthesis of 6-alpha-amino N-substituted morphinans. In particular, the invention provides processes for the reductive amination of 6-keto N-substituted morphinans by catalytic hydrogen transfer.

  本发明提供了用于立体选择性合成6-α-氨基N-取代吗啡烷的过程。特别地，本发明提供了通过催化氢转移还原胺化6-酮基N-取代吗啡烷的过程。
• US8519133B2
  申请人：——

  公开号：US8519133B2

  公开（公告）日：2013-08-27