4-(4-bromo-2-nitro-phenyl)-1-tert-butoxycarbonyl-piperazine | 474329-57-2

• 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: 4-(4-bromo-2-nitro-phenyl)-1-tert-butoxycarbonyl-piperazine
• 英文别名: Tert-butyl 4-(4-bromo-2-nitrophenyl)piperazine-1-carboxylate
• CAS: 474329-57-2
• 化学式: C₁₅H₂₀BrN₃O₄
• 分子量: 386.245
• InChiKey: SSRDVUJPBHVBFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319

反应信息

• 作为反应物：
  描述：

  4-(4-bromo-2-nitro-phenyl)-1-tert-butoxycarbonyl-piperazine 在 dppf-Pd(II) 吡啶 、 1,1'-双(二苯基膦)二茂铁 、 potassium dihydrogenphosphate 、 potassium acetate 、 锌 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 108.5h， 生成 tert-butyl 4-{2-[(2-oxo-2H-chromene-3-)amido]-4-phenylphenyl}piperazine-1-carboxylate
  参考文献：
  名称：

  Naphthyl and Coumarinyl Biarylpiperazine Derivatives as Highly Potent Human β-Secretase Inhibitors. Design, Synthesis, and Enzymatic BACE-1 and Cell Assays

  摘要：

  Twenty novel beta-secretase inhibitors containing biarylpiperazine moieties belonging to naphthyl and coumarinyl series were designed for their potential use in Alzheimer's disease therapy. Enzymatic and cell-based assays have been carried out. The biological results clearly demonstrate that specific substituents located at the N-4-position of the piperazine ring result in excellent in vitro inhibitory potency (IC50 values ranging between 40 and 70 nM). Variable temperature NMR and modeling studies are consistent with the obtained biological data, since these studies confirmed that introduction at the N-4-position of the piperazine ring allows productive interactions within the BACE-1 active site, which appear to be determinative for high BACE-1 inhibitory activity. These results are of particular interest since some of the new analogues belonging to the naphthyl series are almost one log more active than the best inhibitor of the similar family recently reported.

  DOI：

  10.1021/jm0602864
• 作为产物：
  描述：

  2,5-二溴硝基苯 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 异丙醇 为溶剂， 反应 20.0h， 生成 4-(4-bromo-2-nitro-phenyl)-1-tert-butoxycarbonyl-piperazine
  参考文献：
  名称：

  作为潜在抗阿尔茨海默病药物的亚氨基-2H-铬烯衍生物：设计、合成、生物学评价和计算机研究

  摘要：

  合理设计和合成了一系列新的亚氨基-2 H-色烯衍生物作为抗阿尔茨海默病的新型多功能药物。一组苯基亚氨基-2 H-色烯以及新合成的亚氨基色烯衍生物被评估为 BACE1、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 抑制剂。结果表明，在亚氨基色素组中，带有氟苄基部分的10c是最有效的 BACE1 抑制剂，IC 50值为 6.31 μM。体外抗胆碱能活性表明，带有苄基侧基的化合物10a是 AChE（30 μM 时抑制百分比=24.4）和 BuChE（IC 50= 3.3 微米）。还进行了化合物10a针对 BuChE的动力学分析，并显示出混合型抑制模式。神经保护评估显示，化合物11b是一种具有羟乙基部分的苯基亚氨基-2 H-色烯衍生物，在 25 μM 时对 Aβ 诱导的 PC12 神经元细胞损伤提供 32.3% 的保护。此外，针对 BACE1 和 BuChE 的最有效化合物的对接和模拟研究证实了实验结果。

  DOI：

  10.1002/cbdv.202100599

文献信息

• Inhibitors of bace
  申请人：——

  公开号：US20030095958A1

  公开（公告）日：2003-05-22

  The present invention relates to inhibitors of aspartic proteinases, particularly, BACE. The present invention also relates to compositions thereof and methods therewith for inhibiting BACE activity in a mammal, and for treating Alzheimer's Disease and other BACE-mediated diseases.

  本发明涉及天冬氨酸蛋白酶抑制剂，特别是BACE。本发明还涉及其组合物和方法，用于在哺乳动物中抑制BACE活性，并用于治疗阿尔茨海默病和其他BACE介导的疾病。
• [EN] 3-(PYRAZOLYL)-1H-PYRROLO[2,3-b]PYRIDINE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE 3-(PYRAZOLYL)-1H-PYRROLO[2,3-B]PYRIDINE EN TANT QU'INHIBITEURS DE KINASE
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2014006554A1

  公开（公告）日：2014-01-09

  The present application relates to novel 3-(pyrazolyl)-lH-pyrrolo[2,3-b]pyridine derivatives of formula (I), as protein kinase inhibitors. The invention particularly relates to compounds of formula (I), preparation of compounds and pharmaceutical compositions thereof. The invention further relates to pharmaceutically acceptable salts and compositions comprising the said novel 3-(pyrazolyl)-lH-pyrrolo[2,3-b]pyridine derivatives and their use in the treatment of various disorders.

  本申请涉及一种新型的3-(吡唑基)-lH-吡咯并[2,3-b]吡啶衍生物，其化学式为(I)，作为蛋白激酶抑制剂。该发明特别涉及化合物的化学式(I)、化合物的制备以及其药物组成。该发明还涉及药用可接受的盐和组合物，包括所述新型的3-(吡唑基)-lH-吡咯并[2,3-b]吡啶衍生物及其在治疗各种疾病中的应用。
• [EN] NEW ARYL IMIDAZOLES AND RELATED COMPOUNDS AS C5A RECEPTOR MODULATORS<br/>[FR] ARYL IMIDAZOLES ET COMPOSES ASSOCIES, MODULATEURS DE RECEPTEUR C5A
  申请人：NEUROGEN CORP

  公开号：WO2003082829A1

  公开（公告）日：2003-10-09

  The invention provides Aryl substituted imidazoles, pyrazoles, pyridizines and related compounds of the Formula (I) where the ring system represented by Formula (A) is a 5 membered heteroaryl ring system, in which x is 0, A is chosen from carbon and heteroatoms nitrogen, oxygen, and sulfur, and E and G are independently carbon or nitrogen, provided that the 5 membered heteroaryl ring system does not contain more than 3 heteroatoms or more than 1 oxygen or sulfur atom, or a 6 membered heteroaryl ring system, in which x is 1, A, B, E, and G are independently chosen from carbon and nitrogen, provided that the 6 membered heteroaryl ring system does not contain more than 3 nitrogen atoms. The remaining variables, Ar1, Ar2, R, R1, R2, R3, R4, R5, R6, y and z are defined herein. Such compounds are ligands of C5a receptors. Preferred compounds of the invention act bind to C5a receptors with high affinity and exhibit neutral antagonist or inverse agonist activity at C5a receptors. This invention also relates to pharmaceutical compositions comprising such compounds. It further relates to the use of such compounds in treating a variety of inflammatory and immune system disorders.

  该发明提供了式（I）中的芳基取代咪唑、吡唑、吡啶和相关化合物，其中由式（A）表示的环系统是一个5成员杂芳基环系统，在该环系统中x为0，A从碳和杂原子氮、氧和硫中选择，E和G分别为碳或氮，前提是5成员杂芳基环系统不含超过3个杂原子或超过1个氧或硫原子，或者是一个6成员杂芳基环系统，在该环系统中x为1，A、B、E和G分别从碳和氮中选择，前提是6成员杂芳基环系统不含超过3个氮原子。其余变量Ar1、Ar2、R、R1、R2、R3、R4、R5、R6、y和z在此处定义。这些化合物是C5a受体的配体。该发明的优选化合物具有高亲和力结合到C5a受体，并且在C5a受体上表现为中性拮抗剂或逆激动剂活性。该发明还涉及包含这些化合物的药物组合物。它进一步涉及使用这些化合物治疗各种炎症和免疫系统疾病。
• 3-(Pyrazolyl)-1H-Pyrrolo[2,3-b]Pyridine Derivatives as Kinase Inhibitors
  申请人：Aurigene Discovery Technologies Limited

  公开号：US20150336949A1

  公开（公告）日：2015-11-26

  The present application relates to novel 3-(pyrazolyl)-1H-pyrrolo[2,3-b]pyridine derivatives of formula (I), as protein kinase inhibitors. The invention particularly relates to compounds of formula (I), preparation of compounds and pharmaceutical compositions thereof. The invention further relates to pharmaceutically acceptable salts and compositions comprising the said novel 3-(pyrazolyl)-1H-pyrrolo[2,3-b]pyridine derivatives and their use in the treatment of various disorders.

  本申请涉及一种新型的3-(吡唑基)-1H-吡咯[2,3-b]吡啶衍生物，其为蛋白激酶抑制剂。本发明特别涉及化合物(I)的制备、化合物的制备和制药组合物。本发明还涉及药学上可接受的盐和组成物，包括所述新型3-(吡唑基)-1H-吡咯[2,3-b]吡啶衍生物及其在治疗各种疾病中的用途。
• [EN] COMPOUND USED AS WDR5 INHIBITOR OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND USE OF COMPOUND<br/>[FR] COMPOSÉ UTILISÉ EN TANT QU'INHIBITEUR DE WDR5 OU SEL PHARMACEUTIQUEMENT ACCEPTABLE DE CELUI-CI, ET UTILISATION DU COMPOSÉ<br/>[ZH] 一种用作WDR5抑制剂的化合物或其可药用盐及其应用
  申请人：[en]GAN & LEE PHARM CO LTD;[zh]甘李药业股份有限公司

  公开号：WO2024002379A1

  公开（公告）日：2024-01-04

  提供了一种用作WDR5抑制剂的化合物或其可药用盐及该化合物在制备药物中的应用。所述化合物对WDR5具有较高的亲和度，且相比现有技术具有更高的抑制活性。