tert-butyl 4-(4-cyano-3-nitrophenyl)piperazine-1-carboxylate | 1027345-15-8

• 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-(4-cyano-3-nitrophenyl)piperazine-1-carboxylate
• CAS: 1027345-15-8
• 化学式: C₁₆H₂₀N₄O₄
• 分子量: 332.359
• InChiKey: ZHRBYCAJRNNXCR-UHFFFAOYSA-N

物化性质

• 沸点：
  519.4±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-cyano-3-nitrophenyl)piperazine-1-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 四(三苯基膦)钯 盐酸 、 copper(l) iodide 、 氯化亚砜 、 水 、 铁粉 、 sodium carbonate 、 caesium carbonate 、 溶剂黄146 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 乙二醇二甲醚 、 乙醇 、 氯仿 、 乙二醇甲醚 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 22.92h， 生成 N-(7-[4-fluorophenyl]quinazolin-4-yl)-4-((1-(phenylthio)ethan-2-yl)amino)-3-nitrobenzenesulfonamide
  参考文献：
  名称：

  [EN] ARYLSULFONAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  [FR] COMPOSÉS ARYLSULFONAMIDES, COMPOSITIONS ET PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2009143246A3
• 作为产物：
  描述：

  N-(3-bromophenyl)-2-hydroxyiminacetamide 在 2,6-二甲基吡啶 、 三氟甲磺酸酐 、 硫酸 、 盐酸羟胺 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.17h， 生成 tert-butyl 4-(4-cyano-3-nitrophenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  Synthesis and Dual D₂ and 5-HT_1A Receptor Binding Affinities of 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones

  摘要：

  一系列新的7-哌嗪基和7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮已被合成。所述化合物在结构上与阿多拉嗪相关，后者是一种潜在的不典型抗精神病药物，具有强效的D2受体拮抗剂和5-HT1A受体激动剂特性。制备了适当修饰的芳基溴化物，并与叔丁基哌嗪-1-羧酸酯缩合，得到高级中间体哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。同样，Suzuki-Miyaura交叉偶联反应中，环状乙烯基硼酸盐与适当的芳基溴化物反应，得到哌啶基-3,4-二氢喹唑啉-2(1H)-酮。通过哌嗪基和哌啶基-3,4-二氢喹唑啉-2(1H)-酮与适当设计的联芳基醛的还原胺化反应，完成了这些目标化合物的合成。所述化合物被筛选为D2和5-HT1A受体结合亲和力。结构-活性关系研究表明，环戊烯基吡啶和环戊烯基苄基对这些化合物的双重D2和5-HT1A受体结合亲和力有显著贡献。

  DOI：

  10.2174/15734064113096660046

文献信息

• Dihydroquinone derivatives of piperidine and piperazine
  申请人：King Fahd University of Petroleum and Minerals

  公开号：US08916704B1

  公开（公告）日：2014-12-23

  The dihydroquinone derivatives of piperidine and piperazine are 7-piperazinyl and 7-piperadinyl-3,4-dihydroquinazolin-2(1H)-ones that exhibit D2 and 5-HT1A receptor binding affinities, making them suitable for use as the active ingredient of pharmaceuticals for the treatment of schizophrenia. The derivatives have the general formula: where X is carbon or nitrogen and R is a group selected from a through f having the formula: or a pharmaceutically acceptable salt thereof. The piperazine compounds are prepared by condensing 4-bromo-2-nitro-benzonitrile with 1-Boc-piperazine (1-tert-butoxycarbonyl-piperazine) to form an intermediate that is converted to a piperazinyl-3,4-dihydroquinazolin-2(1H)-one. Subsequent reductive amination with the biarylaldehydes a through f completes the synthesis of the 7-piperazinyl-3,4-dihydroquinazolin-2(1H)-ones. The piperadinyl compounds are prepared from tert-butyl-4-(2-oxo-1,2,3,4-tetradihydroquinazolin-7-yl)piperidine-1-carboxylate, which is converted to 7-(piperidin-4-yl)-3,4-dihyroquinazolin-2(1H)-one. Subsequent reductive amination with the biarylaldehydes a through f completes the synthesis of the 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones.

  哌啶和哌嗪的二氢喹啉衍生物是7-哌嗪基和7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮，具有D2和5-HT1A受体结合亲和力，使它们适合用作治疗精神分裂症的药物的活性成分。这些衍生物具有一般公式：其中X是碳或氮，R是从a到f的具有以下结构的基团：或其药用可接受的盐。哌嗪化合物通过将4-溴-2-硝基苯腈与1-Boc-哌嗪(1-叔丁氧羰基-哌嗪)缩合制备，形成一个中间体，该中间体转化为哌嗪基-3,4-二氢喹唑啉-2(1H)-酮。随后与二芳基醛a至f进行还原胺化反应，完成了7-哌嗪基-3,4-二氢喹唑啉-2(1H)-酮的合成。哌啶化合物是从叔丁基-4-(2-氧代-1,2,3,4-四氢喹唑啉-7-基)哌啶-1-羧酸酯制备的，将其转化为7-(哌啶-4-基)-3,4-二羟喹唑啉-2(1H)-酮。随后与二芳基醛a至f进行还原胺化反应，完成了7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮的合成。
• ARYLSULFONAMIDE COMPOUNDS
  申请人：Baell Jonathan Bayldon

  公开号：US20100056517A1

  公开（公告）日：2010-03-04

  The invention relates generally to small molecules that mimic the biological activity of certain peptides and proteins, to compositions containing them and to their use. In particular, the invention relates to compounds of the general formula (I) that mimic the biological activity of BH3-only proteins and are capable of binding to and neutralizing pro-survival Bcl-2 proteins: wherein A 1 , A 2 , B 1 , B 2 , B 3 , X, Z, R 1 , R 2 , R 3 and t are as described herein. The invention also relates to processes of preparing the benzenesulfonamide compounds that mimic portions of peptides and proteins, and to the use of such compounds in the regulation of cell death and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death.

  本发明涉及一般性地模拟某些肽和蛋白质的生物活性的小分子，包括含有它们的组合物以及它们的用途。特别地，本发明涉及一般式（I）的化合物，它们模拟BH3-仅有蛋白质的生物活性，并且能够结合和中和前生存的Bcl-2蛋白质：其中A1、A2、B1、B2、B3、X、Z、R1、R2、R3和t如本文所述。本发明还涉及制备模拟肽和蛋白质部分的苯磺酰胺化合物的过程，以及在调节细胞死亡和治疗和/或预防与细胞死亡失调相关的疾病或状况中使用这些化合物的用途。
• DIHYDROQUINONE DERIVATIVES OF PIPERIDINE AND PIPERAZINE
  申请人：KING FAHD UNIVERSITY OF PETROLEUM AND MINERALS

  公开号：US20150094467A1

  公开（公告）日：2015-04-02

  The dihydroquinone derivatives of piperidine and piperazine are 7-piperazinyl and 7-piperadinyl-3,4-dihydroquinazolin-2(1H)-ones that exhibit D 2 and 5-HT 1A receptor binding affinities, making them suitable for use as the active ingredient of pharmaceuticals for the treatment of schizophrenia. The derivatives have the general formula: where X is carbon or nitrogen and R is a group selected from a through f having the formula: or a pharmaceutically acceptable salt thereof. The piperazine compounds are prepared by condensing 4-bromo-2-nitro-benzonitrile with 1-Boc-piperazine (1-tert-butoxycarbonyl-piperazine) to form an intermediate that is converted to a piperazinyl-3,4-dihydroquinazolin-2(1H)-one. Subsequent reductive amination with the biarylaldehydes a through f completes the synthesis of the 7-piperadinyl-3,4-dihydroquinazolin-2(1H)-ones. The piperadinyl compounds are prepared from tert-butyl-4-(2-oxo-1,2,3,4-tetradihydroquinazolin-7-yl)piperidine-1-carboxylate, which is converted to 7-(piperidin-4-yl)-3,4-dihyroquinazolin-2(1H)-one. Subsequent reductive amination with the biarylaldehydes a through f completes the synthesis of the 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones.

  哌啶和哌嗪的二氢喹啉衍生物是7-哌嗪基和7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮，具有D2和5-HT1A受体结合亲和力，适合用作治疗精神分裂症的药物的活性成分。这些衍生物的通用公式为：其中X为碳或氮，R为从a到f的选择性基团，其公式为：或其药学上可接受的盐。哌嗪类化合物是通过将4-溴-2-硝基苯腈与1-Boc-哌嗪(1-叔丁氧羰基哌嗪)缩合形成中间体，然后转化为哌嗪基-3,4-二氢喹唑啉-2(1H)-酮来制备的。随后，与双芳基醛a到f进行还原胺化反应，完成了7-哌嗪基-3,4-二氢喹唑啉-2(1H)-酮的合成。哌啶类化合物是从叔丁基-4-(2-氧代-1,2,3,4-四氢喹唑啉-7-基)哌啶-1-羧酸酯开始制备的，该化合物转化为7-(哌啶-4-基)-3,4-二氢喹唑啉-2(1H)-酮。随后，与双芳基醛a到f进行还原胺化反应，完成了7-哌啶基-3,4-二氢喹唑啉-2(1H)-酮的合成。
• Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity
  作者：Brad E. Sleebs、Peter E. Czabotar、Wayne J. Fairbrother、W. Douglas Fairlie、John A. Flygare、David C. S. Huang、Wilhelmus J. A. Kersten、Michael F. T. Koehler、Guillaume Lessene、Kym Lowes、John P. Parisot、Brian J. Smith、Morey L. Smith、Andrew J. Souers、Ian P. Street、Hong Yang、Jonathan B. Baell

  DOI：10.1021/jm101596e

  日期：2011.3.24

  ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-xL that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.
• WO2008/61208
  申请人：——

  公开号：——

  公开（公告）日：——