tert-butyl 4-(1-benzyl-1H-indol-4-yl)piperazine-1-carboxylate | 1427173-56-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(1-benzyl-1H-indol-4-yl)piperazine-1-carboxylate
• CAS: 1427173-56-5
• 化学式: C₂₄H₂₉N₃O₂
• 分子量: 391.513
• InChiKey: ALCHFPNEWFXNOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.75
• 重原子数：
  29.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  37.71
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(1-benzyl-1H-indol-4-yl)piperazine-1-carboxylate 在 盐酸 、 potassium carbonate 、 potassium iodide 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 反应 48.0h， 生成 2-(3-(4-(1-benzyl-1H-indol-4-yl)piperazin-1-yl)propyl)-isoindoline-1,3-dione
  参考文献：
  名称：

  具有 5-羟色胺 5-HT 6 拮抗剂、丁酰胆碱酯酶抑制剂和抗氧化活性的抗阿尔茨海默多靶点配体

  摘要：

  血清素 5-HT6 受体、丁酰胆碱酯酶 (BuChE) 和氧化应激与阿尔茨海默病的病理生理学有关。BuChE 的抑制提供了对该疾病的对症治疗，并且在临床试验中证明了 5-HT 6 拮抗剂具有相同的效果。氧化应激被认为是导致阿尔茨海默病发展的主要和主要因素；因此，抗氧化剂可能具有缓解疾病的作用。结合 BuChE 抑制、5-HT 6 拮抗作用和抗氧化特性，可能会产生多靶标配体，提供具有神经保护活性的认知增强特性。在筛选BuChE 5-HT 6 拮抗剂库的基础上，我们选择了两种化合物并设计了它们的结构修饰，以提高 BuChE 抑制活性。我们合成了两个系列的化合物，并测试了它们对 5-HT 6 受体的亲和力和功能活性、BuChE 抑制活性和抗氧化特性。化合物 12 对 5-HT 6 受体的 K i 和 K b 值分别为 41.8 和 74 nM，对 BuChE 的 IC 50 值为 5 µM，抗氧

  DOI：

  10.1002/ardp.201900041
• 作为产物：
  描述：

  4-(1H-4-吲哚)-哌嗪-1-羧酸叔丁酯 、 溴甲苯 在 18-冠醚-6 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 tert-butyl 4-(1-benzyl-1H-indol-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  具有 5-羟色胺 5-HT 6 拮抗剂、丁酰胆碱酯酶抑制剂和抗氧化活性的抗阿尔茨海默多靶点配体

  摘要：

  血清素 5-HT6 受体、丁酰胆碱酯酶 (BuChE) 和氧化应激与阿尔茨海默病的病理生理学有关。BuChE 的抑制提供了对该疾病的对症治疗，并且在临床试验中证明了 5-HT 6 拮抗剂具有相同的效果。氧化应激被认为是导致阿尔茨海默病发展的主要和主要因素；因此，抗氧化剂可能具有缓解疾病的作用。结合 BuChE 抑制、5-HT 6 拮抗作用和抗氧化特性，可能会产生多靶标配体，提供具有神经保护活性的认知增强特性。在筛选BuChE 5-HT 6 拮抗剂库的基础上，我们选择了两种化合物并设计了它们的结构修饰，以提高 BuChE 抑制活性。我们合成了两个系列的化合物，并测试了它们对 5-HT 6 受体的亲和力和功能活性、BuChE 抑制活性和抗氧化特性。化合物 12 对 5-HT 6 受体的 K i 和 K b 值分别为 41.8 和 74 nM，对 BuChE 的 IC 50 值为 5 µM，抗氧

  DOI：

  10.1002/ardp.201900041

文献信息

• INDOLEAMINE DERIVATIVES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES
  申请人：Kolaczkowski Marcin

  公开号：US20140121216A1

  公开（公告）日：2014-05-01

  Indoleamine derivatives of formula (IA), R 1 represents benzyl unsubstituted or substituted with halogen atom, —OH, or C 1 -C 3 -alkyl; phenylsulphonyl unsubstituted or substituted in the phenyl ring with halogen atom, —OH or C 1 -C 3 -alkyl; G 1 represents phenoxyalkyl, heteroaryloxyalkyl- or heterocyclyloxyalkyl-piperazine moiety; and pharmaceutically acceptable salts and solvates thereof. The compounds may be useful for the treatment and/or prevention of the central nervous system disorders.

  公式（IA）的吲哚胺衍生物，其中R1代表苄基未取代或取代为卤原子，-OH，或C1-C3-烷基；苯磺酰未取代或取代为苯环中的卤原子，-OH或C1-C3-烷基；G1代表苯氧基烷基，杂环氧基烷基-或杂环氧基烷基-哌嗪基；以及其药学上可接受的盐和溶剂合物。这些化合物可能对治疗和/或预防中枢神经系统疾病有用。
• [EN] INDOLEAMINE DERIVATIVES FOR THE TREATMENT OF CENTRAL NERVOUS SYSTEM DISEASES<br/>[FR] DÉRIVÉS INDOLÉAMINE UTILISÉS DANS LE TRAITEMENT DE MALADIES DU SYSTÈME NERVEUX CENTRAL
  申请人：ADAMED SP ZOO

  公开号：WO2013001499A1

  公开（公告）日：2013-01-03

  Indoleamine derivatives of formula (IA), wherein R1 represents benzyl unsubstituted or substituted with halogen atom, -OH, or C1-C3-alkyl; phenylsulphonyl unsubstituted or substituted in the phenyl ring with halogen atom, -OH or C1-C3-alkyl; G1 represents phenoxyalkyl, heteroaryloxyalkyl- or heterocyclyloxyalkyl-piperazine moiety; and pharmaceutically acceptable salts and solvates thereof. The compounds may be useful for the treatment and/or prevention of the central nervous system disorders.

  公式（IA）的吲哚胺衍生物，其中R1表示苯甲基未取代或取代有卤素原子，-OH或C1-C3-烷基；苯磺酰基未取代或在苯环中取代有卤素原子，-OH或C1-C3-烷基；G1表示苯氧基烷基，杂环氧基烷基-或杂环氧基烷基-哌嗪基；以及其药学上可接受的盐和溶解物。该化合物可用于治疗和/或预防中枢神经系统疾病。
• Effects of chronic mild stress on rats selectively bred for behavior related to bipolar disorder and depression
  作者：Ryan Murray、Katherine A. Boss-Williams、Jay M. Weiss

  DOI：10.1016/j.physbeh.2013.05.042

  日期：2013.7

  To test the possibility that chronic mild stress (CMS) might be unreliable in producing its often-intended outcome (i.e., decreased preference for sucrose, hypothesized to represent depression-relevant anhedonia) because it is typically applied to "normal" rats, a CMS procedure was applied to rats that may possess genetic susceptibility to affective disorders, having had been selectively-bred to show behavior indicative of such disorders. These rat lines were: Hyperactive (HYPER) rats, which show characteristics of bipolar disorder, Swim-test Susceptible (SUS) and Swim-test Resistant (RES) rats, being susceptible or resistant to effects of stress in the swim test, Swim High-active (SwHi) and Swim Low-active (SwLo) rats, which innately show high or low activity in the swim test These selectively-bred lines were compared to normal, non-selectively bred (NS) rats. During CMS, HYPER rats, both females and males, as well as RES and SwHi rats, showed reduced consumption of a palatable 2% sucrose solution, and reduced preference for sucrose (vs. water) in comparison to non-stressed rats (no CMS) of the same lines. In contrast, CMS produced no decrease in sucrose consumption or in preference for sucrose in normal NS rats, and actually a caused a slight increase in sucrose consumption and preference in male NS rats. Other measures that indicate depression - food intake and motor activity in the home cage - were also assessed. SwLo and SwHi showed greater sensitivity to having their home-cage ambulatory activity reduced by CMS than did NS rats, but no other such differences relative to NS rats were seen for these other measures; thus, changes in sucrose intake or preference could not be explained by a change in caloric intake. These results suggest that the genetic attributes of animals can influence the outcome of CMS, and that the application of CMS to normal, non-selected rats may account, at least in part, for the unreliability of CMS in decreasing consumption of palatable substances and decreasing preference for such substances. (C) 2013 Published by Elsevier Inc.