2-((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)isoindoline-1,3-dione | 160359-68-2

• 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: 2-((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)isoindoline-1,3-dione
• 英文别名: Naltalimide；2-[(4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,6,7,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]isoindole-1,3-dione
• CAS: 160359-68-2
• 化学式: C₂₈H₂₈N₂O₅
• 分子量: 472.541
• InChiKey: DHAITNWJDOSRBU-IBHWKQIPSA-N

物化性质

• 沸点：
  675.2±55.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  2-((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)isoindoline-1,3-dione 在 ammonium hexanitratocerate 、 potassium carbonate 、 肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 23.0h， 生成 (4R,4aS,7R,7aR,12bS,13S)-7-amino-9-(benzyloxy)-3-(cyclopropylmethyl)-1,2,3,4,5,6,7,7a-octahydro-4aH-4,12-methanobenzofuro[3,2-e]isoquinoline-4a,13-diol
  参考文献：
  名称：

  モルヒナン誘導体及びその医薬用途

  摘要：

  【问题】提供具有末梢型选择性κ-阿片受体作用的化合物。 【解决方案】本发明提供以下式（I）或式（II）所示的吗啡诱导体或其药理学上可接受的酸加成盐。 【选择图】无

  公开号：

  JP2018048093A
• 作为产物：
  描述：

  3-acetoxy-6α,14-dihydroxy-17-(cyclopropylmethyl)-4,5α-epoxymorphinan 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 2-((4R,4aS,7R,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl)isoindoline-1,3-dione
  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。
• ANALGESIC
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1820505A1

  公开（公告）日：2007-08-22

  An analgesic which may be applied to wide variety of pain from various causes is disclosed. The analgesic comprises as an effective ingredient a specific morphinan derivative having a nitrogen containing heterocyclic group, such as comopound 1:

  本发明公开了一种镇痛剂，可用于各种原因引起的各种疼痛。这种镇痛剂的有效成分是一种具有含氮杂环基团的特定吗啡烷衍生物，如化合物 1：
• ANTITUSSIVE AGENT
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1974731A1

  公开（公告）日：2008-10-01

  An antitussive, which can be used for therapy or prophylaxyis of coughing, is disclosed. The antitussive comprises as an effective ingredient a morphinan derivative having a nitrogen-containing cyclic substituent or a pharmaceutically acceptable acid addition salt thereof, having a specific structure, such as the compound below [N-(17-cyclopeopylmethyl-4,5α-epoxy-3,14-dihydroxy-morphinan-6β-yl)-3,4,5,6-tetrahydrophthalimide]. The antitussive has an excellent therapeutic or prophylactic effect against coughing and the side effects thereof are small.

  本发明公开了一种可用于治疗或预防咳嗽的止咳剂。该止咳药的有效成分包括具有含氮环状取代基的吗啡南衍生物或其药学上可接受的酸加成盐，具有特定的结构，例如以下化合物[N-(17-环氧甲酰-4,5α-环氧-3,14-二羟基-吗啡南-6β-基)-3,4,5,6-四氢邻苯二甲酰亚胺]。这种止咳药对咳嗽有很好的治疗或预防效果，而且副作用很小。
• METHOD FOR PRODUCING PHARMACEUTICAL TABLET
  申请人：Toray Industries, Inc.

  公开号：EP2156838A1

  公开（公告）日：2010-02-24

  A process for advantageously producing tablets having an improved release property and an excellent stability to change with time is provided. The process is for producing tablets containing a morphinan compound represented by the Formula (I) below or pharmaceutically acceptable acid addition salt thereof and an acidic substance such as fumaric acid, maleic acid or adipic acid, and characterized in that the morphinan compound or a pharmaceutically acceptable acid addition salt thereof is granulated by wet granulation together with (an) excipient(s) prior to adding the acidic substance thereto.

  本发明提供了一种生产片剂的有利工艺，这种片剂具有更好的释放性能和出色的随时间变化的稳定性。该工艺用于生产含有下式（I）所代表的吗啡烷化合物或其药学上可接受的酸加成盐以及富马酸、马来酸或己二酸等酸性物质的片剂，其特征在于吗啡烷化合物或其药学上可接受的酸加成盐在加入酸性物质之前与（一种或多种）赋形剂一起通过湿法制粒。