(S)-3-oxiranylmethyl-1-phenyl-8-[2-(2-thienylphenyl)ethyl]-1,3,8-triazaspiro[4.5]decan-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (S)-3-oxiranylmethyl-1-phenyl-8-[2-(2-thienylphenyl)ethyl]-1,3,8-triazaspiro[4.5]decan-4-one
• 英文别名: (S)-3-oxiranylmethyl-1-phenyl-8-[2-(2-thien-2-yl-phenyl)-ethyl]-1,3,8-triaza-spiro[4.5]decan-4-one；3-[[(2S)-oxiran-2-yl]methyl]-1-phenyl-8-[2-(2-thiophen-2-ylphenyl)ethyl]-1,3,8-triazaspiro[4.5]decan-4-one
• 化学式: C₂₈H₃₁N₃O₂S
• 分子量: 473.639
• InChiKey: PRZTYQZCSLSYNH-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  67.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-氨丙基)吗啉 、 (S)-3-oxiranylmethyl-1-phenyl-8-[2-(2-thienylphenyl)ethyl]-1,3,8-triazaspiro[4.5]decan-4-one 以 乙醇 为溶剂， 生成 3-[2-(R)-hydroxy-3-(3-morpholin-4-yl-propylamino)-propyl]-1-phenyl-8-[2-(2-thien-2-yl-phenyl)-ethyl]-1,3,8-triazaspiro[4.5]decan-4-one trifluoroacetate
  参考文献：
  名称：

  [EN] HYDROXY ALKYL SUBSTITUTED 1,3,8-TRIAZASPIRO[4.5]DECAN-4-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ORL-1 RECEPTOR MEDIATED DISORDERS
  [FR] DERIVES DE 1,3,8-TRIAZASPIRO[4.5]DECAN-4-ONE A SUBSTITUTION HYDROXYALKYLE UTILES POUR TRAITER DES MALADIES ASSOCIEES AU RECEPTEUR ORL-1

  摘要：

  公开号：

  WO2004022558A3
• 作为产物：
  描述：

  3-溴苯乙醇 在 四(三苯基膦)钯 、 sodium hydride 、 碳酸氢钠 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 、 乙二醇二甲醚 、 二氯甲烷 、 mineral oil 为溶剂， 反应 50.5h， 生成 (S)-3-oxiranylmethyl-1-phenyl-8-[2-(2-thienylphenyl)ethyl]-1,3,8-triazaspiro[4.5]decan-4-one
  参考文献：
  名称：

  A selective small molecule NOP (ORL-1 receptor) partial agonist for the treatment of anxiety

  摘要：

  Small molecule (1) has been identified as a selective partial agonist of Opioid Receptor Like-1 (ORL-1) with potential utility for the treatment of anxiety and other disorders. Nociceptin (orphanin FQ) is an endogenous peptide ligand that binds to ORL-1, however it does not bind the classical delta, mu and kappa opioid receptors with high affinity. The synthesis of 1 involved using a molecular diversity approach, to rapidly advance a library of compounds for biological testing. A lead selective potent partial agonist (35-fold ORL-1/Mu) progressed to ORL-1 (NOP or OP4) proof of concept testing in advanced studies. The synthetic approach and biological data for the related chemical series will be presented. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.015

文献信息

• [EN] 7-ARYL-3,9-DIAZABICYCLO(3.3.1)NON-6-ENE DERIVATIVES AND THEIR USE AS RENIN INHIBITORS IN THE TREATMENT OF HYPERTENSION, CARDIOVASCULAR OR RENAL DISEASES<br/>[FR] DERIVES DE 7-ARYL-3,9-DIAZABICYCLO(3.3.1)NON-6-ENE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE RENINE DANS LE TRAITEMENT DE L'HYPERTENSION, DE MALADIES CARDIOVASCULAIRES OU RENALES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2003093267A1

  公开（公告）日：2003-11-13

  The invention relates to novel 3,9-diazabicyclo[3.3.1]nonene derivatives of formula (I) and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors or renin.

  该发明涉及新型3,9-二氮杂双环[3.3.1]壬烯衍生物（I）及相关化合物，以及它们作为药物组合物中活性成分的用途。该发明还涉及相关方面，包括制备这些化合物的过程、含有这些化合物中的一个或多个的药物组合物，尤其是它们作为肾素抑制剂的用途。
• Hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1receptor mediated disorders
  申请人：——

  公开号：US20040142955A1

  公开（公告）日：2004-07-22

  The present invention is directed to novel hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula 1 wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, panic, dementia, mania, bipolar disorder, substance abuse, neuropathic pain, acute pain, chronic pain, migraine, asthma, cough, psychosis, schizophrenia, epilepsy, hypertension, obesity, eating disorders, cravings, diabetes, cardiac arrhythmia, irritable bowel syndrome, Crohn's disease, urinary incontinence, adrenal disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, for improved cognition or memory and for mood stabilization.

  本发明涉及一种新型的羟基烷基取代的1,3,8-三氮杂螺[4.5]癸烷-4-酮衍生物，其一般式为1，其中所有变量如本文所定义，可用于治疗由ORL-1 G蛋白偶联受体介导的疾病和症状。特别地，本发明的化合物可用于治疗焦虑、抑郁、恐慌、痴呆、躁狂、双相情感障碍、物质滥用、神经病性疼痛、急性疼痛、慢性疼痛、偏头痛、哮喘、咳嗽、精神病、精神分裂症、癫痫、高血压、肥胖症、进食障碍、渴望、糖尿病、心律失常、肠易激综合征、克罗恩病、尿失禁、肾上腺疾病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、阿尔茨海默病，用于改善认知或记忆能力和情绪稳定。
• Hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders
  申请人：Battista Kathleen

  公开号：US20060030577A1

  公开（公告）日：2006-02-09

  The present invention is directed to novel hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, panic, dementia, mania, bipolar disorder, substance abuse, neuropathic pain, acute pain, chronic pain, migraine, asthma, cough, psychosis, schizophrenia, epilepsy, hypertension, obesity, eating disorders, cravings, diabetes, cardiac arrhythmia, irritable bowel syndrome, Crohn's disease, urinary incontinence, adrenal disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, for improved cognition or memory and for mood stabilization.

  本发明涉及一种新的羟基烷基取代的1,3,8-三氮杂螺[4.5]癸酮衍生物，其通式如下： 其中所有变量如本文所定义，可用于治疗由ORL-1 G蛋白偶联受体介导的疾病和病症。更具体地，本发明的化合物可用于治疗焦虑、抑郁、惊恐、痴呆、躁狂、双相障碍、物质滥用、神经病性疼痛、急性疼痛、慢性疼痛、偏头痛、哮喘、咳嗽、精神病、精神分裂症、癫痫、高血压、肥胖症、进食障碍、渴望、糖尿病、心脏心律失常、肠易激综合征、克罗恩病、尿失禁、肾上腺疾病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、阿尔茨海默病，以改善认知或记忆，并用于情绪稳定。
• HYDROXY ALKYL SUBSTITUTED 1,3,8-TRIAZASPIRO[4.5]DECAN-4-ONE DERIVATIVES USEFUL FOR THE TREATMENT OF ORL-1 RECEPTOR MEDIATED DISORDERS
  申请人：BATTISTA Kathleen

  公开号：US20090124614A1

  公开（公告）日：2009-05-14

  The present invention is directed to novel hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives of the general formula wherein all variables are as defined herein, useful in the treatment of disorders and conditions mediated by the ORL-1 G-protein coupled receptor. More particularly, the compounds of the present invention are useful in the treatment of disorders and conditions such as anxiety, depression, panic, dementia, mania, bipolar disorder, substance abuse, neuropathic pain, acute pain, chronic pain, migraine, asthma, cough, psychosis, schizophrenia, epilepsy, hypertension, obesity, eating disorders, cravings, diabetes, cardiac arrhythmia, irritable bowel syndrome, Crohn's disease, urinary incontinence, adrenal disorders, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, for improved cognition or memory and for mood stabilization.

  本发明涉及一种新型的羟基烷基取代的1,3,8-三氮杂螺[4.5]癸酮衍生物，其通式如下：其中所有变量均如本文所定义，可用于治疗由ORL-1 G蛋白偶联受体介导的疾病和症状。更具体地，本发明的化合物可用于治疗焦虑、抑郁、惊恐、痴呆、躁狂、双相情感障碍、物质滥用、神经病性疼痛、急性疼痛、慢性疼痛、偏头痛、哮喘、咳嗽、精神病、精神分裂症、癫痫、高血压、肥胖症、进食障碍、渴望、糖尿病、心律失常、肠易激综合征、克罗恩病、尿失禁、肾上腺疾病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、阿尔茨海默病，以改善认知或记忆，并用于情绪稳定。
• 7-ARYL-3,9-DIAZABICYCLO[3.3.1]NON-6-ENE DERIVATIVES AND THEIR USE AS RENIN INHIBITORS IN THE TREATMENT OF HYPERTENSION, CARDIOVASCULAR OR RENAL DISEASES
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：EP1501830A1

  公开（公告）日：2005-02-02