tert-butyl 4-propyl-3-oxopiperazine-1-carboxylate | 1016538-84-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 4-propyl-3-oxopiperazine-1-carboxylate
• 英文别名: Tert-butyl 3-oxo-4-propylpiperazine-1-carboxylate
• CAS: 1016538-84-3
• 化学式: C₁₂H₂₂N₂O₃
• mdl: MFCD24466483
• 分子量: 242.318
• InChiKey: HHYIKSGSIARWAE-UHFFFAOYSA-N

物化性质

• 沸点：
  362.2±35.0 °C(Predicted)
• 密度：
  1.070±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-propyl-3-oxopiperazine-1-carboxylate 在 三氟乙酸 作用下， 反应 3.0h， 生成 1-丙基哌嗪-2-酮
  参考文献：
  名称：

  Design, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancers

  摘要：

  A series of 2-oxopiperazine, 4-aminomethyl-, 3-amino- and 3-aminomethylpiperidine analogues of DM235 (sunifiram) and MN19 (sapunifiram), two previously reported potent cognition-enhancers, have been synthesized and tested in the mouse passive-avoidance test. The compounds display minimal effective doses in the range 0.3-10 mg/kg. Although the new substances do not show improved activity when compared to the parent compounds, some useful information has been obtained to understand structure-activity relationships. In addition, the 3-aminopiperidine moiety appears to be a promising scaffold to synthesize new drugs endowed with cognition-enhancing activity. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.050
• 作为产物：
  描述：

  methyl N-allyl-N-(tert-butoxycarbonyl)glycinate 在 sodium cyanoborohydride 、 臭氧 作用下， 以 甲醇 为溶剂， 生成 tert-butyl 4-propyl-3-oxopiperazine-1-carboxylate
  参考文献：
  名称：

  [EN] PIPERAZINYL ANTIVIRAL AGENTS
  [FR] AGENTS ANTI-VIRAUX À BASE DE PIPÉRAZINYLE

  摘要：

  公开号：

  WO2011041713A3

文献信息

• 含有哌嗪酮的喹唑啉酮类PARP-1/2抑制剂 及其制备方法、药物组合物和用途
  申请人：中国医学科学院药物研究所

  公开号：CN107098886B

  公开（公告）日：2020-07-14

  本发明公开了一类新的含有哌嗪酮的喹唑啉‑2,4(1H,3H)‑二酮类PARP‑1/2抑制剂、及其制法和药物组合物与用途。具体而言，本发明涉及通式I所示的含有哌嗪酮的喹唑啉‑2,4(1H,3H)‑二酮类衍生物及其可药用盐，及其制备方法，含有一个或多个该类化合物的组合物，和该类化合物在制备、预防和/或治疗与PARP‑1/2相关的疾病药物中的用途。
• [EN] CYCLIC AMINE BASE-1 INHIBITORS HAVING A HETEROCYCLIC SUBSTITUENT<br/>[FR] INHIBITEURS D'AMINES CYCLIQUES BACE-1 RENFERMANT UN SUBSTITUANT HETEROCYCLIQUE
  申请人：SCHERING CORP

  公开号：WO2005014540A1

  公开（公告）日：2005-02-17

  Disclosed are novel compounds of the formula (I)or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is formula (I) X is -0-, -C(R14)2- or -N(R)-; Z is -C(R14)2- or -N(R)-; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, -CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, -OR35, -N(R24)(R25) or -SR35; R41 is alkyl, cycloalkyl, -S02(alkyl), -C(O)-alkyl, -C(O)-cycloalkyl or -alkyl-NH-C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula (I). Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

  揭示了具有以下结构的新化合物（I）或其药学上可接受的盐或溶剂，其中R1为结构（I），X为-0-，-C(R14)2-或-N(R)-；Z为-C(R14)2-或-N(R)-；t为0、1、2或3；每个R和R2独立地为H、烷基、环烷基、环烷基烷基、芳基、杂环芳基、杂环烷基、芳基烷基、杂环芳基烷基、杂环烷基烷基、烯基或炔基；每个R14为H、烷基、烯基、炔基、卤素、-CN、卤代烷基、环烷基、环烷基烷基、芳基、杂环芳基、芳基烷基、杂环芳基烷基、杂环烷基烷基、-OR35、-N(R24)(R25)或-SR35；R41为烷基、环烷基、-S02(烷基)、-C(O)-烷基、-C(O)-环烷基或-烷基-NH-C(O)CH3；其余变量如规范中所定义。还揭示了包括化合物的药物组合物（I）的制剂以及使用化合物（I）治疗认知或神经退行性疾病的方法。还揭示了包括化合物（I）的药物组合物和治疗方法，其与治疗认知或神经退行性疾病有用的其他药剂结合使用。
• [EN] BIARYL INHIBITORS OF THE SODIUM CHANNEL<br/>[FR] INHIBITEURS BIARYLE DU CANAL SODIQUE
  申请人：ZALICUS PHARMACEUTICALS LTD

  公开号：WO2013131018A1

  公开（公告）日：2013-09-06

  The invention relates to compounds useful in treating conditions associated with voltage- gated ion channel function, particularly conditions associated with sodium channel activity. More specifically, the invention concerns biaryl derivatives (e.g., compounds according to any of Formulas (I)-(XII) or Compounds (l)-(372) of Table 1) that are that are useful in treatment of conditions such as epilepsy, cancer, pain, migraine, Parkinson's Disease, mood disorders, schizophrenia, psychosis, tinnitus, amyotropic lateral sclerosis, glaucoma, ischaemia, spasticity disorders, obsessive compulsive disorder, restless leg syndrome and Tourette syndrome.

  该发明涉及与电压门控离子通道功能相关的化合物，特别是与钠通道活性相关的病症。更具体地说，该发明涉及联萘衍生物（例如，根据表1的任一公式（I）-（XII）或化合物（l）-（372）的化合物），这些化合物可用于治疗癫痫、癌症、疼痛、偏头痛、帕金森病、情绪障碍、精神分裂症、精神病、耳鸣、肌萎缩性侧索硬化、青光眼、缺血、痉挛性障碍、强迫症、不安腿综合征和抽动症等病症的治疗。
• CYCLIC AMINE BACE-1 INHIBITORS HAVING A HETEROCYCLIC SUBSTITUENT
  申请人：Cumming Jared N.

  公开号：US20090312341A1

  公开（公告）日：2009-12-17

  Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is X is —O—, —C(R 14 ) 2 — or —N(R)—; Z is —C(R 14 ) 2 — or —N(R)—; t is 0, 1, 2 or 3; each R and R 2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R 14 is H, alkyl, alkenyl, alkynyl, halo, —CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, —OR 35 , —N(R 24 ) (R 25 ) or —SR 35 ; R 41 is alkyl, cycloalkyl, —SO 2 (alkyl), —C(O)-alkyl, —C(O)-cycloalkyl or -alkyl-NH—C(O)CH 3 ; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula I. Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

  本发明涉及公式I的新化合物或其药学上可接受的盐或溶剂，其中R1为X为—O—，—C（R14）2—或—N（R）—；Z为—C（R14）2—或—N（R）—；t为0、1、2或3；每个R和R2独立地为H，烷基，环烷基，环烷基烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基，烯基或炔基；每个R14为H，烷基，烯基，炔基，卤素，—CN，卤代烷基，环烷基，环烷基烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基，—OR35，—N（R24）（R25）或—SR35；R41为烷基，环烷基，—SO2（烷基），—C（O）-烷基，—C（O）-环烷基或-烷基-NH-C（O）CH3；其余变量如规范中所定义。本发明还涉及包含公式I化合物的制药组合物以及使用公式I化合物治疗认知或神经退行性疾病的方法。本发明还涉及包含公式I化合物的制药组合物和治疗方法，其中该组合物与其他对治疗认知或神经退行性疾病有用的药物一起使用。
• Discovery of Quinazoline-2,4(1<i>H</i>,3<i>H</i>)-dione Derivatives Containing a Piperizinone Moiety as Potent PARP-1/2 Inhibitors─Design, Synthesis, <i>In Vivo</i> Antitumor Activity, and X-ray Crystal Structure Analysis
  作者：Jie Zhou、Tingting Du、Xiaoyu Wang、Haiping Yao、Jialing Deng、Yan Li、Xiaoguang Chen、Li Sheng、Ming Ji、Bailing Xu

  DOI：10.1021/acs.jmedchem.3c01152

  日期：2023.10.26

  PARP-1/2 inhibitors have become an important therapeutic strategy for the treatment of HR-deficient tumors. However, discovery of new inhibitors with an improved and distinct pharmacological file still need enormous explorations. Herein, a series of novel highly potent PARP-1/2 inhibitors bearing an N-substituted piperazinone moiety were achieved. In particular, Cpd36 was identified as a distinct PARP

  PARP-1/2抑制剂已成为治疗HR缺陷型肿瘤的重要治疗策略。然而，发现具有改进且独特的药理学文件的新抑制剂仍需要大量探索。在此，获得了一系列带有N-取代哌嗪酮部分的新型高效PARP-1/2抑制剂。特别是，Cpd36被确定为一种独特的 PARP 抑制剂，不仅对 PARP-1 (IC 50 = 0.94 nM) 和 PARP-2 (IC 50 = 0.87 nM) 表现出显着的酶活性，而且对 PARP-7 (IC 50 = 0.87 nM) 也表现出显着的酶活性。 0.21 nM)，并且比其他 PARP 同工型具有高选择性。此外，Cpd36具有口服生物利用度，并且在乳腺癌和前列腺癌异种移植模型中显着抑制肿瘤生长。PARP-1和PARP-2中Cpd36的晶体结构以及PARP-7中预测的结合模式揭示了其结合特征，并为进一步开发高效和选择性的PARP-1和/或PARP-7抑制剂提供了深刻的信息。