(9R,13R,14S)-17-(cyclopropylmethyl)-3,14-dihydroxymorphinan-6-one | 26989-39-9

• 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: (9R,13R,14S)-17-(cyclopropylmethyl)-3,14-dihydroxymorphinan-6-one
• 英文别名: (4bR,8aS,9R)-11-(cyclopropylmethyl)-3,8a-dihydroxy-8,8a,9,10-tetrahydro-5H-9,4b-(epiminoethano)phenanthren-6(7H)-one；Morphinan-6-one, 17-(cyclopropylmethyl)-3,14-dihydroxy-；(1R,9R,10S)-17-(cyclopropylmethyl)-4,10-dihydroxy-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5-trien-13-one
• CAS: 26989-39-9
• 化学式: C₂₀H₂₅NO₃
• 分子量: 327.423
• InChiKey: JKSUUZMNWGEVRC-VAMGGRTRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (9R,13R,14S)-17-(cyclopropylmethyl)-3,14-dihydroxymorphinan-6-one 在 potassium cyanide 、 ammonium hydroxide 、 potassium carbonate 、 氯化铵 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (1R,9R,10S,13S)-13-amino-17-(cyclopropylmethyl)-4-hydroxy-11-oxa-17-azapentacyclo[7.5.3.210,13.01,10.02,7]nonadeca-2(7),3,5-trien-12-one
  参考文献：
  名称：

  [EN] OPIOID RECEPTOR MODULATING OXABICYCLO[2.2.2]OCTANE MORPHINANS
  [FR] MORPHINANES OXABICYCLO[2.2.2]OCTANE MODULATEURS DES RÉCEPTEURS AUX OPIACÉS

  摘要：

  该申请涉及公式（I）的化合物及其药用可接受的盐和溶剂化合物，其中R1、R2、Y、Z和G的定义如规范中所述。该发明还涉及使用公式（I）的化合物及其药用可接受的盐和溶剂化合物来治疗对一种或多种阿片受体调节敏感的疾病，或作为合成中间体。本发明的某些化合物特别适用于治疗疼痛。

  公开号：

  WO2015097545A1
• 作为产物：
  描述：

  (4bR,8aS,9R)-11-(cyclopropylmethyl)-8a-hydroxy-3-methoxy-8,8a,9,10-tetrahydro-5H-9,4b-(epiminoethano)phenanthren-6(7H)-one 在 三溴化硼 、 ammonium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 1.33h， 以70%的产率得到(9R,13R,14S)-17-(cyclopropylmethyl)-3,14-dihydroxymorphinan-6-one
  参考文献：
  名称：

  Synthesis and evaluation of novel opioid ligands with a C-homomorphinan skeleton

  摘要：

  As the reports about C-homomorphinans with the seven-membered C-ring are much fewer than those of morphinan derivatives with a six-membered C-ring, we attempted to synthesize C-homomorphinan derivatives and to evaluate their opioid activities. C-Homomorphinan 5 showed sufficient binding affinities to the opioid receptors. C-Homomorphinan derivatives possessing the delta address moiety such as indole (NTI-type), quinoline, or benzylidene (BNTX-type) functionalities showed the strongest binding affinities for the delta receptor among the three types of opioid receptors, which indicated that the C-homomorphinan skeleton sufficiently functions as a message-part in the ligand. Although NTI-type compound 8 and quinoline compound 9 with C-homomorphinan scaffold exhibited lower affinities and selectivities for the delta receptor than the corresponding morphinan derivatives did, both the binding affinity and selectivity for the delta receptor of BNTX-type compound 12 with a seven-membered C-ring were improved compared with the corresponding compounds with a six-membered C-ring including BNTX itself. BNTX-Type compound 12 was the most selective d receptor antagonist among the tested compounds. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.040

文献信息

• PREPARATION OF OPIATE ANALGESICS BY REDUCTIVE ALKYLATION
  申请人：Mitchell Melville

  公开号：US20120046466A9

  公开（公告）日：2012-02-23

  A process for preparing a compound of formula (A), (B) or (C): wherein P is H, CH 3 or a hydroxyl protecting group; X is O, a protected ketone, OH, a protected hydroxyl group or H; Y is OH, a protected hydroxyl group or H; W is C(CH 3 ) 2 OH, C(CH 3 )(C(CH 3 ) 3 )OH or COCH 3 ; Z is C 2 -C 10 alkyl or C 2 -C 10 arylalkyl; and is a single bond or a double bond, is disclosed. The process is a reductive alkylation in the presence of hydrogen and a reductive alkylation catalyst.

  一种制备化合物(A)、(B)或(C)的方法：其中P是H、CH3或羟基保护基；X是O、保护酮、OH、保护羟基或H；Y是OH、保护羟基或H；W是C( )2OH、C( )(C( )3)OH或CO ；Z是C2-C10烷基或C2-C10芳基烷基；并且是单键或双键。该方法是在氢气和还原烷基催化剂的存在下进行还原烷基化反应。
• Preparation of Opiate Analgesics by Reductive Alkylation
  申请人：Mitchell Melville

  公开号：US20080045715A1

  公开（公告）日：2008-02-21

  A process for preparing a compound of formula (A), (B) or (C): wherein P is H, CH 3 or a hydroxyl protecting group; X is O, a protected ketone, OH, a protected hydroxyl group or H; Y is OH, a protected hydroxyl group or H; W is C(CH 3 )OH, C(CH 3 )(C(CH 3 ) 3 )OH or COCH 3 ; Z is C 2 -C 10 alkyl or C 2 -C 10 arylalkyl; and ′ is a single bond or a double bond, is disclosed. The process is a reductive alkylation in the presence of hydrogen and a reductive alkylation catalyst.

  一种制备化合物(A)、(B)或(C)的方法：其中P为H、CH3或羟基保护基；X为O、受保护的酮、OH、受保护的羟基或H；Y为OH、受保护的羟基或H；W为C( )OH、C( )(C( )3)OH或CO ；Z为C2-C10烷基或C2-C10芳基烷基；′为单键或双键。该过程是在氢和还原性烷基化催化剂存在下进行的还原性烷基化反应。
• PYRAZOLOMORPHINAN DERIVATIVE
  申请人：The Kitasato Institute

  公开号：EP4062972A1

  公开（公告）日：2022-09-28

  The present invention provides a compound having a selective opioid δ receptor agonist effect. The present invention provides a pyrazolomorphinan derivative represented by general formula (1) (in the formula, (II) R1 represents a hydrogen atom, an alkyl group, a cycloalkylmethyl group, or the like, R2 represents a hydrogen atom or a hydroxy protecting group, R3 represents a hydroxy group, an alkyl group, a partially unsaturated heterocyclic group, an aryl group, a heteroaryl group, or the like; and R4 represents a hydrogen atom, an alkyl group, an aralkyl group, a cycloalkyl group, a cycloalkyl alkyl group, a saturated heterocyclic group, an aryl group, a heteroaryl group, or the like). The pyrazolomorphinan derivative can be used as an active ingredient in an analgesic, an antidepressant, an anxiolytic, or the like.

  本发明提供了一种具有选择性阿片受体δ激动剂作用的化合物。本发明提供了一种由通式（1）表示的吡唑吗啡衍生物（在公式中，(II) R1代表氢原子、烷基、环烷基甲基或类似物，R2代表氢原子或羟基保护基，R3代表羟基、烷基、部分不饱和杂环基、芳基、杂芳基或类似物；R4代表氢原子、烷基、芳基烷基、环烷基、环烷基烷基、饱和杂环基、芳基、杂芳基或类似物）。该吡唑吗啡衍生物可用作镇痛剂、抗抑郁剂、抗焦虑剂等活性成分。
• Enantioselective de novo synthesis of 14-hydroxy-6-oxomorphinans
  作者：Jonathan C. Moore、Louis Modell、Jacqueline R. Glenn、Kieran D. Jones、Stephen P. Argent、J. Robert Lane、Meritxell Canals、Hon Wai Lam

  DOI：10.1039/d4cc01788a

  日期：——

  The enantioselective de novo synthesis of pharmacologically important 14-hydroxy-6-oxomorphinans is described. 4,5-Desoxynaltrexone and 4,5-desoxynaloxone were prepared using this route and their biological activities against the opioid receptors were measured.

  描述了药理学上重要的 14-羟基-6-氧代吗啡喃的对映选择性从头合成。使用该途径制备了 4,5-去氧纳曲酮和 4,5-去氧纳洛酮，并测量了它们针对阿片受体的生物活性。
• US4141897A
  申请人：——

  公开号：US4141897A

  公开（公告）日：1979-02-27