1-(4-methylphenyl)-1,3,8-triazaspiro<4.5>decan-4-one | 1023-87-6

• 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: 1-(4-methylphenyl)-1,3,8-triazaspiro<4.5>decan-4-one
• 英文别名: 1-p-tolyl-1,3,8-triaza-spiro[4.5]decan-4-one；1-Oxo-4-p-tolyl-2,4,8-triazaspiro<4.5>decan；1,3,8-Triazaspiro[4.5]decan-4-one, 1-(4-methylphenyl)-；1-(4-methylphenyl)-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 1023-87-6
• 化学式: C₁₄H₁₉N₃O
• 分子量: 245.324
• InChiKey: FKTLPANFGXXTMF-UHFFFAOYSA-N

物化性质

• 熔点：
  190.0-191.4 °C
• 沸点：
  505.4±50.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-苯基环己酮 、 1-(4-methylphenyl)-1,3,8-triazaspiro<4.5>decan-4-one 在 titanium(IV) isopropylate 、 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 生成 (rac,cis)-8-(2-phenyl-cyclohexyl)-1-p-tolyl-1,3,8-triaza-spiro[4.5]decan-4-one
  参考文献：
  名称：

  Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors

  摘要：

  Screening of the Roche compound library led to the identification of cis-N-(2-phenyt-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.075

文献信息

• [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- -，- - - -，- -0-或-0- -；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、-( )n-环烷基、-( )n-CF3、-( )p-0-较低烷基、-( )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-( )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。
• 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— —，— — — —，— —O—或—O— —；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。
• HETEROCYCLIC COMPOUNDS AS CCR5 ANTAGONISTS
  申请人：AQUINO Christopher Joseph

  公开号：US20090053172A1

  公开（公告）日：2009-02-26

  The present invention relates to compounds of formula (I), or pharmaceutically acceptable derivatives thereof, useful in the treatment of CCR5-related diseases and disorders, for example, useful in the inhibition of HIV replication, the prevention or treatment of an HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).

  本发明涉及式(I)化合物或其药学上可接受的衍生物，用于治疗CCR5相关的疾病和障碍，例如，用于抑制HIV复制，预防或治疗HIV感染，并用于治疗由此导致的获得性免疫缺陷综合症（AIDS）。
• 1,3,8-Triaza-spiro 4,5 decan-4-on derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0921125A1

  公开（公告）日：1999-06-09

  The present invention relates to compounds of the general formula wherein R1is hydrogen, lower alkyl, halogen, lower alkoxy, trifluoromethyl, lower alkyl-phenyl or (C5-7)-cycloalkyl; R2is hydrogen, lower alkyl, phenyl or lower alkyl-phenyl; R3is hydrogen, lower alkyl, benzyl, lower alkyl-phenyl, lower alkyl-diphenyl, triazinyl, cyanomethyl, lower alkyl-piperidinyl, lower alkyl-naphthyl, (C5-7)-cycloalkyl, lower alkyl-(C5-7)-cycloalkyl, lower alkyl-pyridinyl, lower alkyl-morpholinyl, lower alkyl-dioxolanyl, lower alkyl-oxazolyl or lower alkyl-2-oxo-oxazolidinyl and wherein the ring systems may be substituted by additional lower alkyl, lower alkoxy, trifluoromethyl or phenyl, or -(CH2)nC(O)O-lower alkyl, -(CH2)nC(O)NH2, -(CH2)nC(O)N(lower alkyl)2, -(CH2)nOH or -(CH2)nC(O)NHCH2C6H5; R4is hydrogen, lower alkyl or nitrilo; Ais a ring system, consisting of (a) (C5-15)-cycloalkyl, which may be in addition to R4optionally substituted by lower alkyl, trifluoromethyl, phenyl, (C5-7)-cycloalkyl, spiro-undecan-alkyl or by 2-norbornyl, or is one of the following groups dodecahydro-acenaphthylen-1yl (e), bicyclo[6.2.0]dec-9-yl (f) and bicyclononan-9-yl (g); and wherein R5 and R6are hydrogen, lower alkyl or taken together and with the carbon atoms to which they are attached form a phenyl ring; R7is hydrogen or lower alkyl; the dotted line represents an optional bond and nis 1 to 4; and to pharmaceutically acceptable acid addition salts thereof. Compounds of the present invention are agonists and/or antagonists of the Orphanin FQ (OFQ) receptor. Consequently they will be useful in the treatment of memory and attention deficits, psychiatric, neurological and physiological disorders, especially, but not limited to, amelioration of symptoms of anxiety and stress disorders, depression, trauma, memory loss due to Alzheimer's disease or other dementias, epilepsy and convulsions, acute and/or chronic pain conditions, symptoms of addictive drug withdrawal, control of water balance, Na+ excretion, arterial blood pressure disorders and metabolic disorders such as obesity.

  本发明涉及通式如下的化合物 式中 R1是氢、低级烷基、卤素、低级烷氧基、三氟甲基、低级烷基苯基或(C5-7)-环烷基； R2 是氢、低级烷基、苯基或低级烷基苯基； R3是氢、低级烷基、苄基、低级烷基-苯基、低级烷基-二苯基、三嗪基、氰甲基、低级烷基-哌啶基、低级烷基-萘基、（C5-7）-环烷基、低级烷基-（C5-7）-环烷基、低级烷基-吡啶基、低级烷基-吗啉基、低级烷基-二氧戊环基、低级烷基-噁唑基或低级烷基-2-氧代-噁唑烷基，其中环系统可被额外的低级烷基、低级烷氧基、三氟甲基或苯基取代，或被-(CH2)nC(O)O-低级烷基、-( )nC(O)NH2、-( )nC(O)N(低级烷基)2、-( )nOH 或 -( )nC(O)NH C6H5取代； R4 是氢、低级烷基或硝基； A 是一个环状系统，包括 (a) (C5-15)-环烷基，除 R4 外，还可被低级烷基、三氟甲基、苯基、(C5-7)-环 烷基、螺十一烷基或 2-降冰片基取代，或为以下基团之一 十二氢-苊烯-1-基 (e)、双环[6.2.0]癸-9-基 (f) 和双环壬-9-基 (g)； 其中 R5 和 R6 为氢、低级烷基或与它们所连接的碳原子一起形成苯环； R7 为氢或低级烷基； 虚线代表任选键，且 n为 1 至 4； 及其药学上可接受的酸加成盐。 本发明的化合物是孤儿素 FQ（OFQ）受体的激动剂和/或拮抗剂。因此，它们可用于治疗记忆和注意力缺陷、精神、神经和生理疾病，特别是但不限于改善焦虑和应激障碍、抑郁症、创伤、阿尔茨海默病或其他痴呆症引起的记忆丧失、癫痫和抽搐、急性和/或慢性疼痛、成瘾药物戒断症状、控制水平衡、Na+排泄、动脉血压紊乱和代谢紊乱（如肥胖）等症状。
• Examination of a series of 8-[3-[bis(4-fluorophenyl)amino]propyl]-1-aryl-1,3,8-triazaspiro[4.5]decan-4-ones as potential antipsychotic agents
  作者：Lawrence D. Wise、Ian C. Pattison、Donald E. Butler、Horace A. DeWald、Edward P. Lewis、Sandra J. Lobbestael、Haile Tecle、Linda L. Coughenour、David A. Downs、B. P. H. Poschel

  DOI：10.1021/jm00150a011

  日期：1985.12

  8-[3-[Bis(4-fluorophenyl)amino]propyl]-1-phenyl-1,3,8- triazaspiro[4.5]decan-4-one (3) and related compounds have been shown to have antipsychotic profiles in biochemical and behavioral pharmacological test models. The dose of 3 necessary to produce catalepsy in rats is much greater than that required for activity in behavioral tests predictive of antipsychotic efficacy, for example the suppression of high base line medial forebrain bundle self-stimulation in rats. This suggests that 3 would have a reduced propensity for neurological side effects. The effects of substitution on the 1-phenyl moiety and on the N-3 nitrogen atom of the triazaspirodecanone portion of 3 were examined. Results from this study suggest that behavioral activity is sensitive to substituents on the 1-phenyl moiety while substituents on the N-3 nitrogen are more generally tolerated. In both rats and squirrel monkeys compound 3 was found to have a similar separation between doses inhibiting Sidman avoidance activity and those causing catalepsy. However, in an extrapyramidal side effect (EPS) test model using haloperidol-sensitized cebus monkeys, 3 elicited signs of EPS at doses approximating those previously determined to be efficacious.