(4R,4aS,7aR,12bS)-7-benzylimino-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol | 73986-27-3

• 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,7aR,12bS)-7-benzylimino-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol
• CAS: 73986-27-3
• 化学式: C₂₄H₂₆N₂O₃
• 分子量: 390.482
• InChiKey: PVAUYEVADWNDEA-QLBRKBSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  65.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R,4aS,7aR,12bS)-7-benzylimino-3-methyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,9-diol 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 甲醇 为溶剂， 反应 144.0h， 以57%的产率得到alpha-Oxymorphamine Dihydrochloride
  参考文献：
  名称：

  Stereospecific synthesis of the 6.alpha.- and 6.beta.-amino derivatives of naltrexone and oxymorphone

  摘要：

  DOI：

  10.1021/jo01304a051
• 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 carbonate 、 对甲苯磺酸 作用下， 以 水 、 苯 为溶剂， 反应 11.0h， 生成 (4R,4aS,7aR,12bS)-7-benzylimino-3-methyl-2,4,5,6,7a,13-hexahydro-1H-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

• Effects of Substitution on the Pyrrole N Atom in Derivatives of Tetrahydronaltrindole, Tetrahydrooxymorphindole, and a Related 4,5-Epoxyphenylpyrrolomorphinan
  作者：Sanjay K. Srivastava、Shefali、Carl N. Miller、Mario D. Aceto、John R. Traynor、John W. Lewis、Stephen M. Husbands

  DOI：10.1021/jm040817t

  日期：2004.12.1

  The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphina n (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while the TNTI derivatives (7) were potent DOR antagonists or low-efficacy DOR partial

  在四氢萘并三唑（TNTI），四氢吗啉吲哚（TOMI）和17-环丙基甲基-3,14-二羟基-4,5-环氧-4'-苯基-6,7中吡咯和N原子的取代作用：报道了2'，3'-吡咯并吗啡（4）。在阿片样物质功能测定中，有4种是有效的deltaopioid受体（DOR）拮抗剂，而TNTI衍生物（7）是有效的DOR拮抗剂或低效DOR部分激动剂，没有明显的选择性。TOMI衍生物（8）是具有明显选择性的DOR激动剂。在体内证实了7d的DOR拮抗剂活性，但8d的主要激动剂作用是由μ阿片受体介导的。
• Michael Reactions of Benzylimines Derived from Morphinan-6-ones: Synthesis of Pyrrolo- and Pyridinomorphinans
  作者：Shefali、Sanjay K. Srivastava、Lee D. Hall、John W. Lewis、Stephen M. Husbands

  DOI：10.1002/1522-2675(200206)85:6<1790::aid-hlca1790>3.0.co;2-g

  日期：2002.6

  The benzylimines 15 derived from oxymorphones 14 and generated in situ reacted with Michael acceptors (methyl methacrylate, maleic anhydride, and alpha-metlivlene-gamma-butyrolactone) to give opioid ligands 16, 17, and 19-21 having pyrrole- or pyridine-derived ring systems (see Scheme 3). The product of the reaction with maleic anhydride displayed a surprising preference for the 2-hydroxypyrrole form 19 rather than for the tautomeric 1.6-dihydro-2H-pyrrol-2-one form 24, resulting from the stability of the C(6)=C(7) bond in oxymorphone and related structures.
• 4‘-Arylpyrrolomorphinans:  Effect of a Pyrrolo-<i>N</i>-benzyl Substituent in Enhancing δ-Opioid Antagonist Activity
  作者：Sanjay K. Srivastava、Stephen M. Husbands、Mario D. Aceto、Carl N. Miller、John R. Traynor、John W. Lewis

  DOI：10.1021/jm010841w

  日期：2002.1.1

  A new method for the preparation of N-benzylpyrrolomorphinans has been developed. Thus Michael reaction of the benzylimines of oxycodones and oxymorphones with nitrostyrenes gave a series of 4'-aryl-N-benzylpyrrolomorphinans. These were selective delta antagonists of much higher in vitro potency (with 5a having K-e delta = <1 nM) than their binding affinities predicted. In mice in vivo assays 5a showed good delta antagonist activity in the antiwrithing analgesic assay and also inhibited delta agonist-induced convulsant activity.