17-(cyclobutylmethyl)-3,6-dimethoxy-4,5α-epoxy-6,7,8,14-tetradehydromorphinan | 77794-48-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: 17-(cyclobutylmethyl)-3,6-dimethoxy-4,5α-epoxy-6,7,8,14-tetradehydromorphinan
• 英文别名: N-demethyl-N-(cyclobutylmethyl)-thebaine；(4R,7aR,12bS)-3-(cyclobutylmethyl)-7,9-dimethoxy-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline
• CAS: 77794-48-0
• 化学式: C₂₃H₂₇NO₃
• 分子量: 365.472
• InChiKey: DWNONICTGAMUKC-VSDWSMLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  17-(cyclobutylmethyl)-3,6-dimethoxy-4,5α-epoxy-6,7,8,14-tetradehydromorphinan 在 甲酸 、 双氧水 作用下， 反应 6.0h， 以46%的产率得到N-demethyl-N-(cyclobutylmethyl)-14-hydroxycodeinone
  参考文献：
  名称：

  Synthesis of N-Demethyl-N-Substituted-14-Hydroxycodeine and Morphine Derivatives⁺

  摘要：

  A fews representatives (1b-d) of a novel group of structurally related morphine-antagonist compounds have been prepared in stereochemically homogeneous form. The employed procedures involve O-demethylation either of the corresponding codeine derivatives 2b-d, or those of the N-alkylated analogues 2b,c, synthesized from N-demethylthebaine (7a) by means of N-alkylation and subsequent transformations of 7b,d, - compounds selected from the resulting functionalized thebaines 7b-e.

  DOI：

  10.1080/00397919208021649
• 作为产物：
  描述：

  环丁基甲酰氯 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 17-(cyclobutylmethyl)-3,6-dimethoxy-4,5α-epoxy-6,7,8,14-tetradehydromorphinan
  参考文献：
  名称：

  Synthesis of N-Demethyl-N-Substituted-14-Hydroxycodeine and Morphine Derivatives⁺

  摘要：

  A fews representatives (1b-d) of a novel group of structurally related morphine-antagonist compounds have been prepared in stereochemically homogeneous form. The employed procedures involve O-demethylation either of the corresponding codeine derivatives 2b-d, or those of the N-alkylated analogues 2b,c, synthesized from N-demethylthebaine (7a) by means of N-alkylation and subsequent transformations of 7b,d, - compounds selected from the resulting functionalized thebaines 7b-e.

  DOI：

  10.1080/00397919208021649

文献信息

• (+)-morphinans as antagonists of Toll-like receptor 9 and therapeutic uses thereof
  申请人：Mallinckrodt LLC

  公开号：US11142502B2

  公开（公告）日：2021-10-12

  The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat pain. Also provided are pharmaceutical combination compositions comprising a (+)-morphinan and an opioid agonist/monoamine reuptake inhibitor, as well as methods for using the combination compositions to treat pain.

  本发明提供了包含Toll样受体9（TLR9）拮抗剂活性的(+)-吗啡烷，以及使用(+)-吗啡烷治疗疼痛的方法。本发明还提供了包含(+)-吗啡南和阿片激动剂/单胺再摄取抑制剂的药物组合物，以及使用该组合物治疗疼痛的方法。
• Analgesic narcotic antagonists. 6. 7.beta.,8.beta.-Methano- and 7.beta.,8.beta.-epoxydihydrocodeinone
  作者：Michael P. Kotick

  DOI：10.1021/jm00138a016

  日期：1981.6

  Reaction of codeinone (2) with CH2N2 in the presence of Pd(OAc)2 yielded mixtures of starting material and (2) and 7 beta, 8 beta-methanodihydrocodeinone (3). Initial resolution of this mixture was achieved via carbonyl reduction followed by chromatography to give pure 7 beta, 8 beta-methanodihydrocodeine (4), which was oxidized to 3. Reaction of the mixture containing 2 and 3 with mercaptoethanol and NaOH [2 leads to 8 beta-[(hydroxyethyl)thio]dihydrocodeinone (5)] allowed selective crystallization of 3. The beta configuration of the cyclopropane ring in 3 was established by cleavage with aqueous HCl to give the 8 beta-(chloromethyl) compound 6, followed by carbonyl reduction and dehalogenation to 8 beta-methyldihydrocodeine (8). Reaction of the N-(cycloalkylmethyl) derivatives (13 and 18) of 2 with CH2N2/Pd(OA)2 gave potential mixed agonist-antagonists and 14 and 19, which were purified by reduction-oxidation (14) or mercaptoethanol-base treatment (19). Compound 2, on oxidation with alkaline peroxide, gave the previously reported 7 beta, 8 beta-epoxydihydrocodeinone (22) as the hemimethanol ketal (21). Compound 3 was about ninefold more potent an agonist than dihydrocodeine, and the N-(cyclopropylmethyl)-7 beta, 8 beta-methano compound 19 had moderately potent mixed agonist-narcotic antagonist properties.
• (+)-MORPHINANS AS ANTAGONISTS OF TOLL-LIKE RECEPTOR 9 AND THERAPEUTIC USES THEREOF
  申请人：Mallinckrodt LLC

  公开号：US20200172488A1

  公开（公告）日：2020-06-04

  The present invention provides (+)-morphinans comprising Toll-like receptor 9 (TLR9) antagonist activity, as well as methods for using the (+)-morphinans to treat pain. Also provided are pharmaceutical combination compositions comprising a (+)-morphinan and an opioid agonist/monoamine reuptake inhibitor, as well as methods for using the combination compositions to treat pain.
• Synthesis of N-Demethyl-N-Substituted-14-Hydroxycodeine and Morphine Derivatives⁺
  作者：Sándor Hosztafi、Csaba Simon、Sándor Makleit

  DOI：10.1080/00397919208021649

  日期：1992.9

  A fews representatives (1b-d) of a novel group of structurally related morphine-antagonist compounds have been prepared in stereochemically homogeneous form. The employed procedures involve O-demethylation either of the corresponding codeine derivatives 2b-d, or those of the N-alkylated analogues 2b,c, synthesized from N-demethylthebaine (7a) by means of N-alkylation and subsequent transformations of 7b,d, - compounds selected from the resulting functionalized thebaines 7b-e.