1-(4-氯苯基)-1,3,8-三氮螺[4.5]癸烷-4-酮 | 61271-84-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 1-(4-氯苯基)-1,3,8-三氮螺[4.5]癸烷-4-酮
• 英文名称: 1-(4-chlorophenyl)-1,3,8-triazaspiro[4.5]-decan-4-one
• 英文别名: 1-(p-chlorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one；1-(4-Chlorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 61271-84-9
• 化学式: C₁₃H₁₆ClN₃O
• 分子量: 265.743
• InChiKey: PSTZLFWHHJKOJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  1-(4-氯苯基)-1,3,8-三氮螺[4.5]癸烷-4-酮 在 正丁基锂 、 pyridine-SO3 complex 、 TEA 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 1-(4-Chloro-phenyl)-8-[(1R,2R)-2-(4-fluoro-phenyl)-2-hydroxy-cyclohexyl]-1,3,8-triaza-spiro[4.5]decan-4-one
  参考文献：
  名称：

  Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile

  摘要：

  During SAR exploration of N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of an hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the mu opioid receptors was achieved. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.067
• 作为产物：
  描述：

  8-benzyl-1-(4-chlorophenyl)-1,3,8-triazaspiro[4.5]decan-4-one 在 10% palladium on carbon 、 氢气 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 生成 1-(4-氯苯基)-1,3,8-三氮螺[4.5]癸烷-4-酮
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Halogenated N-(2-(4-Oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-8-yl)ethyl)benzamides: Discovery of an Isoform-Selective Small Molecule Phospholipase D2 Inhibitor

  摘要：

  Phospholipase D (PLD) catalyzes the conversion of phosphatidylcholine to the lipid second messenger phosphatidic acid. Two mammalian isoforms of PLD have been identified, PLD I and PLD2, which share 53% sequence identity and are subject to different regulatory mechanisms. Inhibition of PLD enzymatic activity leads to increased cancer cell apoptosis, decreased cancer cell invasion, and decreased metastasis of cancer cells; therefore, the development of isoform-specific, PLD inhibitors is a novel approach for the treatment of cancer. Previously, we developed potent dual PLD1/PLD2, PLD1-specific (> 1700-fold selective), and moderately PLD2-preferring (> 10-fold preferring) inhibitors. Here, we describe a matrix library strategy that afforded the most potent (PLD2 IC(50) = 20 nM) and selective (75-fold selective versus PLD1) PLD2 inhibitor to date. N-(2-(1-(3-fluorophenyl)-4-oxo-1.3.8-triazaspiro[4.5]decan-8-yl)ethyl)-2-naphthamide (22a), with an acceptable DMPK profile. Thus, these new isoform-selective PLD inhibitors will enable researchers to dissect the signaling roles and therapeutic potential of individual PLD isoforms to an unprecedented degree.

  DOI：

  10.1021/jm100814g

文献信息

• [EN] TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS<br/>[FR] TRIAZA-SPIRODÉCANONES UTILISÉES EN TANT QU'INHIBITEURS DE DDR1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017005583A1

  公开（公告）日：2017-01-12

  The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.

  本发明涉及式(I)的化合物或其药用盐，其中L和R1至R5如本文所述，以及它们的制备方法、包含它们的药物组合物，以及它们作为药物的用途。
• [EN] TRIAZA-SPIROPIPERIDINE DERIVATIVES FOR USE AS GLYT-1 INHIBITORS IN THE TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS<br/>[FR] DERIVES DE TRIAZA-SPIROPIPERIDINE A UTILISER COMME INHIBITEURS DE GLYT-1 DANS LE TRAITEMENT DE TROUBLES NEUROLOGIQUES ET NEUROPSYCHIATRIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005040166A1

  公开（公告）日：2005-05-06

  The invention relates to compounds of the general formula (I), wherein A-A is -CH2-CH2-, -CH2-CH2-CH2-, -CH2-0- or -0-CH2-; x is hydrogen or hydroxy; R1 is aryl or heteroaryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkoxy, halogen or trifluoromethyl; R2 is aryl or heteroaryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkoxy, halogen or trifluoromethyl, or is lower alkyl, -(CH2)n-­cycloalkyl, -(CH2)n-CF3, -(CH2)p-0-lower alkyl, -(CH2)1,2-phenyl, optionally substituted by halogen, lower alkyl, lower alkoxy or trifluoromethyl, or is -(CH2)p-NRR', wherein W and R' form together with the N-atom a heterocyclic ring, selected from the group consisting of piperidine, morpholine, thiomorpholine or 1, I-dioxo thiomorpholine; R3, R4 are independently from each other hydrogen, lower alkyl, phenyl or benzyl; R5 is hydrogen, lower alkyl or benzyl; R6 is hydrogen or lower alkyl; n is 0, 1 or 2; and p is 2 or 3; and to pharmaceutically acceptable acid addition salts thereof for the treatment of psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

  该发明涉及一般式(I)的化合物，其中A-A为-CH2-CH2-，-CH2-CH2-CH2-，-CH2-0-或-0-CH2-；x为氢或羟基；R1为芳基或杂环芳基，未取代或由一个或多个取代基取代，所选取自较低烷基、较低烷氧基、卤素或三氟甲基的群组；R2为芳基或杂环芳基，未取代或由一个或多个取代基取代，所选取自较低烷基、较低烷氧基、卤素或三氟甲基的群组，或为较低烷基、-(CH2)n-环烷基、-(CH2)n-CF3、-(CH2)p-0-较低烷基、-(CH2)1,2-苯基，或者可由卤素、较低烷基、较低烷氧基或三氟甲基取代的苯基，或为-(CH2)p-NRR'，其中W和R'与N原子一起形成选自哌啶、吗啉、硫代吗啉或1,1-二氧硫代吗啉的杂环环的环；R3、R4相互独立为氢、较低烷基、苯基或苄基；R5为氢、较低烷基或苄基；R6为氢或较低烷基；n为0、1或2；p为2或3；以及其药用可接受的酸盐，用于治疗精神病、疼痛、记忆和学习中的神经退行性功能障碍、精神分裂症、痴呆症和其他认知过程受损的疾病，如注意力缺陷障碍或阿尔茨海默病。
• Indol-3-yl-carbonyl-azaspiro derivatives
  申请人：Bissantz Caterina

  公开号：US20070072888A1

  公开（公告）日：2007-03-29

  This invention relates to indol-3-yl-carbonyl-azaspiro derivatives which act as V1a receptor antagonists and which are represented by Formula I: wherein the azaspiro-head group A and the residues R 1 , R 2 and R 3 are as defined herein. The invention further relates to pharmaceutical compositions containing such compounds, their use for treating dysmenorrhea, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, obsessive compulsive disorder, anxiety and depressive disorders, and methods of preparation thereof.

  本发明涉及一种表示为式I的indol-3-yl-carbonyl-azaspiro衍生物，其作为V1a受体拮抗剂，其中azaspiro头基团A和残基R1，R2和R3如此定义。本发明还涉及含有这种化合物的制药组合物，其用于治疗痛经、高血压、慢性心力衰竭、不适当的加压素分泌、肝硬化、肾病综合征、强迫症、焦虑和抑郁症，并且涉及其制备方法。
• Triaza-spiropiperidine derivatives
  申请人：Ceccarelli Maria Simona

  公开号：US20050107373A1

  公开（公告）日：2005-05-19

  The invention relates to compounds of the general formula wherein A-A is —CH 2 —CH 2 —, —CH 2 —CH 2 —CH 2 —, —CH 2 —O— or —O—CH 2 —; and X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , n, and p are as defined herein, or a pharmaceutically acceptable salt thereof for the treatment of psychoses, pain, neurodegenerative dysfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

  本发明涉及一般式化合物，其中A-A为—CH2—CH2—，—CH2—CH2—CH2—，—CH2—O—或—O—CH2—；X、R1、R2、R3、R4、R5、R6、n和p如本文所定义，或其药学上可接受的盐，用于治疗精神病、疼痛、记忆和学习的神经退行性功能障碍、精神分裂症、痴呆症和其他认知过程受损的疾病，如注意力缺陷障碍或阿尔茨海默病。
• Triazaspirodecanylmethylindolon-Derivate
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0273168A1

  公开（公告）日：1988-07-06

  Es werden Verbindungen der Formel worin R₁ Wasserstoff, niederes Alkyl oder Acyl, R₂ und R₃ unabhängig voneinander je niederes Alkyl, Aralkyl oder Alkenyl, oder R₂ und R₃ zuammen einen Ring mit 5-8 Kohlenstoffatomen, R₄ Phenyl, substi­tuiertes Phenyl, Cyclohexyl, substituiertes Cyclohexyl, Cyclopentyl, substituiertes Cyclopentyl, Cycloheptyl oder substituiertes Cycloheptyl, R₅ Wasserstoff oder niederes Alkyl und R₆ Wasserstoff, niederes Alkyl oder Acyl bedeuten, und pharmazeutisch annehmbare Säureadditionssalze davon be­schrieben. Die Verbindungen der Formel I und die pharmazeu­tisch annehmbaren Säureadditionssalze davon sind anti-­emetische Wirkstoffe, welche keine Nebenwirkungen auf das Zentralnervensystem zeigen.

  式中的化合物 其中 R₁ 是氢、低级烷基或酰基，R₂ 和 R₃ 各自独立地是低级烷基、芳基或烯基，或 R₂ 和 R₃ 共同形成具有 5-8 个碳原子的环，R₄ 是苯基、取代的苯基、环己基、取代的环己基、环戊基、取代的环戊基、环庚基或取代的环庚基、环己基、取代的环己基、环戊基、取代的环戊基、环庚基或取代的环庚基， R₅ 是氢或低级烷基，R₆ 是氢、低级烷基或酰基、 及其药学上可接受的酸加成盐。式 I 化合物及其药学上可接受的酸加成盐是对中枢神经系统无副作用的止吐药。