N-(17-allyl-4,5α-epoxy-3,14-dihydroxy-morphinan-6β-yl)-phthalimide | 160359-67-1

• 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-(17-allyl-4,5α-epoxy-3,14-dihydroxy-morphinan-6β-yl)-phthalimide
• 英文别名: 2-[(4R,4aS,7R,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]isoindole-1,3-dione
• CAS: 160359-67-1
• 化学式: C₂₇H₂₆N₂O₅
• 分子量: 458.514
• InChiKey: WSEBPQDMWRPPMX-KQIADLJUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  90.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(17-allyl-4,5α-epoxy-3,14-dihydroxy-morphinan-6β-yl)-phthalimide 在 hydrazine hydrate 、 顺-2-戊烯醇 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 N-((4R,4aS,7R,7aR,12bS)-3-allyl-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)-4-azido-3-iodobenzamide
  参考文献：
  名称：

  用于放射光亲和标记细胞系和小鼠脑中阿片受体的 IBNtxA 叠氮基芳基类似物的合成和表征。

  摘要：

  Mu 阿片受体 (MOR-1) 介导临床使用的阿片类药物（如吗啡、羟考酮和芬太尼）的生物学作用。μ 阿片受体基因 OPRM1 经历广泛的选择性剪接，产生多个剪接变体。一种类型的剪接变体是仅包含六个跨膜结构域 (6TM) 的截短变体，可介导新型阿片类药物（例如 3'-碘苯甲酰纳曲胺 (IBNtxA)）的镇痛作用。以前，我们已经证明 IBNtxA 是一种有效的镇痛剂，对一系列疼痛模型有效，但没有许多与传统阿片类药物相关的副作用。为了调查 IBNtxA 标记的目标，我们合成了 IBNtxA 的两种芳基叠氮基类似物，它们允许对转染细胞系中的小鼠 mu 阿片受体 (mMOR-1) 和可能包含小鼠大脑中 6TM 位点的 mMOR-1 蛋白复合物进行光标记。我们证明了 IBNtxA 的烯丙基和炔烃芳基叠氮基衍生物在细胞系和 MOR-1 蛋白复合物外源或内源性表达以及在小鼠大脑中发现的有效放射性光标记 m

  DOI：

  10.1007/s10571-020-00867-6
• 作为产物：
  描述：

  [(4R,4aS,7S,7aR,12bS)-4a,7-dihydroxy-3-prop-2-enyl-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] acetate 在 盐酸羟胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 乙醇 、 水 、 苯 为溶剂， 反应 1.17h， 生成 N-(17-allyl-4,5α-epoxy-3,14-dihydroxy-morphinan-6β-yl)-phthalimide
  参考文献：
  名称：

  Stereoselective synthesis of β-naltrexol, β-naloxol β-naloxamine, β-naltrexamine and related compounds by the application of the mitsunobu reac

  摘要：

  As a continuation of our work, aimed at adopting the Mitsunobu reaction in the morphine series, a few representatives of dihydroisocodeines and dihydroisomorphines and their 14 beta-hydroxy analogues were prepared. p-Nitrobenzoic acid was used as carboxylic acid and the prepared esters were cleaved to obtain the title compounds. Using phthalimide as acidic component several new 6 beta-phthalimidodihydromorphine and dihydrocodeine derivatives and their 14 beta-hydroxy analogues have been synthesized. Cleavage of the phthalimido derivatives with hydrazine hydrate afforded the corresponding 6 beta-amino derivatives.

  DOI：

  10.1016/s0040-4020(01)85541-1

文献信息

• Remedies or preventives for urinary frequency or urinary incontinence and morphinan derivatives having nitrogen-containing heterocyclic group
  申请人：Izumimoto Naoki

  公开号：US20060040970A1

  公开（公告）日：2006-02-23

  The invention provides a morphinan derivative of the Formula (I): (wherein R 1 is methyl, cyclopropylmethyl or the like; R 2 and R 3 are hydroxy, methoxy, acetoxy or the like; both Y and Z are valence bonds, —C(═O)— or the like; X is C 2 -C 5 carbon chain (one of the carbon atoms may be substituted by oxygen, sulfur or nitrogen) constituting a part of the ring structure, or the like; (R 4 ) k is substituted or non-substituted benzene fused ring, carbonyl group or the like; R 9 is hydrogen or the like; R 10 and R 11 are bound to represent —O—, or the like, and R 6 is hydrogen or the like) or a pharmaceutically acceptable acid addition salt thereof. The invention also provides a therapeutic or prophylactic agent for urinary frequency or urinary incontinence, comprising as an effective ingredient the morphinan derivative or the pharmaceutically acceptable acid addition salt thereof; a method for therapy or prophylaxis of the diseases.

  该发明提供了一种公式（I）的吗啡类衍生物： 其中，R1为甲基、环丙甲基或类似物；R2和R3分别为羟基、甲氧基、乙酰氧基或类似物；Y和Z均为价键、-C（═O）-或类似物；X为C2-C5碳链（其中一个碳原子可以被氧、硫或氮取代）构成环结构的一部分或类似物；（R4）k为取代或非取代苯融合环、羰基基团或类似物；R9为氢或类似物；R10和R11被结合表示为-O-或类似物，R6为氢或类似物，或其药学上可接受的酸加成盐。该发明还提供了一种治疗或预防尿频或尿失禁的药物，其有效成分为吗啡类衍生物或其药学上可接受的酸加成盐；以及治疗或预防该疾病的方法。
• REMEDIES OR PREVENTIVES FOR URINARY FREQUENCY OR URINARY INCONTINENCE AND MORPHINAN DERIVATIVES HAVING NITROGEN-CONTAINING HETEROCYCLIC GROUP
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1555266A1

  公开（公告）日：2005-07-20

  The invention provides a morphinan derivative of the Formula (I): [wherein R1 is methyl, cyclopropylmethyl or the like; R2 and R3 are hydroxy, methoxy, acetoxy or the like; both Y and Z are valence bonds, -C(=O)- or the like; X is C2-C5 carbon chain (one of the carbon atoms may be substituted by oxygen, sulfur or nitrogen) constituting a part of the ring structure, or the like; (R4)k is substituted or non-substituted benzene fused ring, carbonyl group or the like; R9 is hydrogen or the like; R10 and R11 are bound to represent -O-, or the like, and R6 is hydrogen or the like] or a pharmaceutically acceptable acid addition salt thereof. The invention also provides a therapeutic or prophylactic agent for urinary frequency or urinary incontinence, comprising as an effective ingredient the morphinan derivative or the pharmaceutically acceptable acid addition salt thereof; a method for therapy or prophylaxis of the diseases, and use for the diseases. The compounds of the invention are useful as a new therapeutic or prophylactic agent for urinary frequency or urinary incontinence, free from side effects, and useful for the method for therapy or prophylaxis of the diseases and for use for the diseases.

  本发明提供了一种式（I）的吗啡烷衍生物： [其中 R1 是甲基、环丙基甲基或类似物；R2 和 R3 是羟基、甲氧基、乙酰氧基或类似物；Y 和 Z 都是价键、-C(＝O)- 或类似物；X 是构成环结构一部分的 C2-C5 碳链（其中一个碳原子可被氧、硫或氮取代）或类似物；(R4)k是取代或非取代的苯融合环、羰基或类似物；R9是氢或类似物；R10和R11结合代表-O-或类似物，R6是氢或类似物]或其药学上可接受的酸加成盐。本发明还提供了一种治疗或预防尿频或尿失禁的药物，其有效成分包括吗啡烷衍生物或其药学上可接受的酸加成盐；一种治疗或预防疾病的方法，以及疾病的用途。 本发明的化合物可作为尿频或尿失禁的新型治疗剂或预防剂，无副作用，并可用于疾病的治疗或预防方法以及疾病的用途。
• REMEDIES OR PREVENTIVES FOR URINARY INCONTINENCE AND MORPHINAN DERIVATIVES HAVING NITROGEN-CONTAINING HETEROCYCLIC GROUP
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1555266B1

  公开（公告）日：2014-05-21
• Anti-Itching Agent
  申请人：Izumimoto Naoki

  公开号：US20080275074A1

  公开（公告）日：2008-11-06

  A novel antipruritic useful for the treatment of pruritus accompanying various diseases is disclosed. The antipruritic comprises a specific morphinan derivative having a nitrogen-containing cyclic group or the pharmaceutically acceptable acid addition salt thereof such as N-(17-cyclopropylmethyl-4,5α-epoxy-3,14-dihydroxy-morphinan-6β-yl)-phthalimide hydrochloric acid salt or N-(17-cyclopropylmethyl-4,5α-epoxy-3,14-dihydroxy-morphinan-6β-yl)-3,4,5,6-tetrahydrophthalimide tartaric acid salt.
• US7320984B2
  申请人：——

  公开号：US7320984B2

  公开（公告）日：2008-01-22