1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one | 256640-45-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one
• 英文别名: J 113397；1-[(3R,4R)-1-(cyclooctylmethyl)-3-(hydroxymethyl)piperidin-4-yl]-3-ethylbenzimidazol-2-one
• CAS: 256640-45-6
• 化学式: C₂₄H₃₇N₃O₂
• 分子量: 399.577
• InChiKey: MBGVUMXBUGIIBQ-LEWJYISDSA-N

物化性质

• 熔点：
  145-145.5 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  518.5±43.0 °C(Predicted)
• 密度：
  1.109±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO: 2mg/mL, clear

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-叔丁氧羰基-L-丙氨酸 、 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 以0.64 g的产率得到[(3R,4R)-1-(cyclooctylmethyl)-4-(3-ethyl-2-oxobenzimidazol-1-yl)piperidin-3-yl]methyl (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate
  参考文献：
  名称：

  Improved Synthesis of the ORL Antagonist 1-[(3R,4R)-1-Cyclooctylmethyl-3-ethoxycarbonyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397)

  摘要：

  A practical synthesis of optically pure 1-[(3R,4R)-1-cyclooctylmethyl-3-ethoxycarbonyl-4-piperidinyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one (J-113397) was developed that avoids the use of chiral columns.

  DOI：

  10.1080/00397910801997579
• 作为产物：
  描述：

  盐酸-4-哌啶酮-3-羧酸乙酯 在 palladium on activated charcoal 乙酸铵 、 lithium aluminium tetrahydride 、 氢气 、 三乙酰氧基硼氢化钠 、 sodium hydride 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one
  参考文献：
  名称：

  Discovery of the First Potent and Selective Small Molecule Opioid Receptor-like (ORL1) Antagonist:  1-[(3R,4R)-1-Cyclooctylmethyl-3- hydroxymethyl-4-piperidyl]-3-ethyl- 1,3-dihydro-2H-benzimidazol-2-one (J-113397)

  摘要：

  DOI：

  10.1021/jm990517p

文献信息

• [EN] BUPRENORPHINE ANALOGS<br/>[FR] ANALOGUES DE BUPRÉNORPHINE
  申请人：PURDUE PHARMA LP

  公开号：WO2012038813A1

  公开（公告）日：2012-03-29

  The present invention is directed to Buprenorphine Analog compounds of the Formula (I), Formula (IA) or Formula (IB) shown below, wherein R1, R2, R8, R 3a, R 3b, G, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

  本发明涉及如下所示的公式(I)、公式(IA)或公式(IB)的丁丙诺啡类似物化合物，其中R1、R2、R8、R 3a、R 3b、G、X、Z和Y的定义如本文所述。本发明的化合物可用于治疗疼痛、便秘以及通过阿片类和ORL-1受体的活性调节的其他状况。
• N-dihydroxyalkyl-substituted 2-oxo-imidazole derivatives
  申请人：Hashimoto Masaya

  公开号：US20070015792A1

  公开（公告）日：2007-01-18

  The invention provides the compounds represented by the formula (I) in which, R stands for a dihydroxy-substituted C 1 -C 6 alkyl group, and Cy stands for an optionally substituted C 6 -C 10 bi- or tri-cyclic aliphatic carbocyclic group. These compounds act as nociceptin receptor antagonist, and are useful, for example, as relievers against tolerance to narcotic analgesic, dependence on narcotic analgesic or addiction; analgesic enhancers; antiobestic or appetite suppressors; treating or prophylactic agents for cognitive impairment and dementia/amnesia; agents for treating developmental cognitive abnormality; remedy for schizophrenia; agents for treating neurodegenerative diseases; anti-depressant or treating agents for affective disorder; treating or prophylactic agents for diabetes insipidus; treating or prophylactic agents for polyuria; and remedy for hypotension and the like.

  该发明提供了由式(I)表示的化合物，其中R代表二羟基取代的C1-C6烷基基团，Cy代表一个可选择取代的C6-C10双环或三环脂肪环碳环基团。这些化合物作为痛觉受体拮抗剂，例如，可用作缓解对麻醉镇痛药的耐受性、对麻醉镇痛药的依赖或成瘾的药物；镇痛增强剂；抗肥胖或食欲抑制剂；治疗或预防认知障碍和失忆症/健忘症的药物；治疗发育性认知异常的药物；治疗精神分裂症的药物；治疗神经退行性疾病的药物；抗抑郁或治疗情感障碍的药物；治疗或预防尿崩症的药物；治疗或预防多尿症的药物；以及治疗低血压等的药物。
• Benzomorphan Analogs and the Use Thereof
  申请人：LOCKMAN Jeffrey

  公开号：US20140135351A1

  公开（公告）日：2014-05-15

  The present invention is directed to Benzomorphan Analog compounds of the Formula I″, Formula IA″, Formula IB″, Formula IC″, or Formula ID″ as shown below; and related Formula I′, Formula IA′, Formula IB′, Formula IC′, or Formula ID′; Formula I, Formula IA, Formula IB, Formula IC, or Formula ID; wherein R 1 , R 2a , R 2b , R 3 and R 4 are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

  本发明涉及以下所示的Formula I″、Formula IA″、Formula IB″、Formula IC″或Formula ID″的苯吗啡类似物化合物；以及相关的Formula I′、Formula IA′、Formula IB′、Formula IC′或Formula ID′；Formula I、Formula IA、Formula IB、Formula IC或Formula ID；其中R1、R2a、R2b、R3和R4如本文所定义。本发明的化合物可用于治疗疼痛、便秘以及受阿片类和ORL-1受体活性调节的其他疾病。
• A New Synthetic Approach to 1-[(3R,4R)-1-Cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1,3-dihydro-benzimidazol-2-one (J-113397), the first non-peptide ORL-1 receptor antagonist
  作者：Carmela De Risi、Gian Piero Pollini、Claudio Trapella、Ilaria Peretto、Silvano Ronzoni、Giuseppe A.M. Giardina

  DOI：10.1016/s0968-0896(01)00085-2

  日期：2001.7

  Dieckmann cyclization of the Michael adduct 8 of cyclooctylmethylamine to methyl acrylate, condensation with o-phenylendiamine produced the beta-enamino ester 2, which has been conveniently used to construct the benzimidazolone substituent at C-4. Catalytic hydrogenation of intermediate 11 followed by base-promoted cis--trans isomerization of the key compound 12 led to the formation of ester 13, which was

  一种有效的方法来处理1-[（（3R，4R）-1-环辛基甲基-3-羟甲基-4-哌啶基] -3-乙基-1,3-二氢苯并咪唑-2-酮（J-113397）1，第一个概述了文献中描述的非肽ORL-1受体拮抗剂。通过环辛基甲胺的迈克尔加成物8的Dieckmann环化成丙烯酸甲酯构造哌啶骨架后，与邻苯二胺缩合生成β-烯胺酯2，该酯已被方便地用于在C-4处构建苯并咪唑酮取代基。中间体11的催化加氢反应，然后通过碱促进的关键化合物12的顺式-反式异构化反应，导致形成酯13，该酯通过LiAlH（4）还原转化为外消旋标题化合物。
• BUPRENORPHINE ANALOGS
  申请人：Kyle Donald J.

  公开号：US20140057931A1

  公开（公告）日：2014-02-27

  The present invention is directed to Buprenorphine Analog compounds of the Formula (I), Formula (IA) or Formula (IB) shown below, wherein R 1 , R 2 , R 8 , R 3a , R 3 b , G, X, Z and Y are as defined herein. Compounds of the Invention are useful for treating pain, constipation, and other conditions modulated by activity of opioid and ORL-1 receptors.

  本发明涉及以下式子所示的哌啶酯类似物化合物，其中R1、R2、R8、R3a、R3b、G、X、Z和Y如本文所定义。本发明的化合物可用于治疗疼痛、便秘和其他受到阿片类和ORL-1受体活性调节的病症。