5-methoxy-2-(piperidin-1-yl)aniline | 438249-87-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 5-methoxy-2-(piperidin-1-yl)aniline
• 英文别名: 1-(4-Methoxy-2-aminophenyl)piperidine；5-methoxy-2-piperidin-1-ylaniline
• CAS: 438249-87-7
• 化学式: C₁₂H₁₈N₂O
• mdl: MFCD09754373
• 分子量: 206.288
• InChiKey: KQLGPEOFPYOBBX-UHFFFAOYSA-N

物化性质

• 沸点：
  374.7±32.0 °C(Predicted)
• 密度：
  1.097±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-(piperidin-1-yl)aniline 在 甲烷磺酸 、 双氧水 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 1.0h， 以75%的产率得到7-methoxy-1,2,3,4-tetrahydro-benzo[4,5]imidazo[1,2-a]pyridine
  参考文献：
  名称：

  在乙酸乙酯中使用过氧化氢将脂环族稠合苯并咪唑和抗肿瘤苯并咪唑醌进行更环保的合成

  摘要：

  使用环境友好且经济高效的乙酸乙酯中的过氧化氢，无需有机水萃取和色谱法即可从商业邻-（吡咯烷基-1-基）苯胺制备高收率的吡咯并[1,2- a ]苯并咪唑。用吡啶[1,2- a ]苯并咪唑所需的甲磺酸，以高收率相似地获得了六，七和八元环稠合的类似物。通过3,6-二甲氧基-2-（环氨基）苯胺的环化，可以高产率获得抗肿瘤苯并咪唑醌衍生物。

  DOI：

  10.1016/j.tetlet.2017.07.102
• 作为产物：
  描述：

  1-(4-甲氧基-2-硝基-苯基)-哌啶 在 氯化铵 、 锌 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以20 mg的产率得到5-methoxy-2-(piperidin-1-yl)aniline
  参考文献：
  名称：

  具有中等至缓慢作用红细胞阶段活性的 2-(N-苯基甲酰胺) 三唑并嘧啶抗疟药的优化

  摘要：

  疟疾是由从该属的寄生虫毁灭性的寄生虫病疟原虫。据报道，所有临床上可用的抗疟药都存在治疗耐药性，威胁到我们控制疾病的能力，因此持续需要开发新型抗疟药。为了实现这一目标，我们从 Janssen Jumpstarter 库的高通量筛选中针对恶性疟原虫的无性阶段鉴定了 2-（N-苯基甲酰胺）三唑并嘧啶类寄生虫。在这里，我们描述了已识别类别的结构活性关系和无性阶段活性的优化，同时保持对人 HepG2 细胞系的选择性。本研究中最有效的类似物显示出对恶性疟原虫多药耐药菌株和诺氏疟原虫无性寄生虫的等效活性。无性阶段表型研究确定三唑并嘧啶类在滋养体阶段捕获寄生虫，但这些寄生虫很可能在第二个无性周期之前仍然具有代谢活性，因此具有中度至缓慢的作用开始。在体外观察到中心羧酰胺的非 NADPH 依赖性降解和低水溶性ADME 分析。一个重大挑战仍然是纠正这些缺陷，以进一步推进 2-( N-苯基甲酰胺) 三唑并嘧啶支架

  DOI：

  10.1016/j.bioorg.2021.105244

文献信息

• Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof
  申请人：Cytovia, Inc.

  公开号：US20030069239A1

  公开（公告）日：2003-04-10

  The present invention is directed to substituted 2-aryl-4-arylaminopyrimidine and analogs thereof, represented by the general Formula I: 1 wherein A, Ar 1 , Ar 2 , R 1 and R 3 are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. The compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及被一般式I所代表的取代的2-芳基-4-芳基氨基嘧啶及其类似物： 其中A，Ar1，Ar2，R1和R3在此处被定义。本发明还涉及发现具有式I的化合物是caspase的激活剂和凋亡诱导剂。本发明的化合物可用于诱导在出现未受控制的异常细胞生长和扩散的各种临床病况中的细胞死亡。
• Positioning of an unprecedented 1,5-oxaza spiroquinone scaffold into SMYD2 inhibitors in epigenetic space
  作者：Lama Prema Dhorma、Mahesh K. Teli、Bhargav Gupta Nangunuri、Arramshetti Venkanna、Rao Ragam、Arunkranthi Maturi、Anvar Mirzaei、Dang-Khoa Vo、Han-Joo Maeng、Mi-hyun Kim

  DOI：10.1016/j.ejmech.2021.113880

  日期：2022.1

  Lysine methyltransferases are important regulators of epigenetic signaling and are emerging as a novel drug target for drug discovery. This work demonstrates the positioning of novel 1,5-oxaza spiroquinone scaffold into selective SET and MYND domain-containing proteins 2 methyltransferases inhibitors. Selectivity of the scaffold was identified by epigenetic target screening followed by SAR study for

  赖氨酸甲基转移酶是表观遗传信号的重要调节剂，并且正在成为药物发现的新药物靶点。这项工作证明了将新型 1,5-恶氮螺醌支架定位到选择性 SET 和 MYND 结构域的蛋白质 2 甲基转移酶抑制剂中。支架的选择性通过表观遗传靶点筛选确定，然后对支架进行 SAR 研究。通过由迭代合成和计算研究（对接、元动力学模拟）组成的两步​​优化迭代地执行优化。计算结合研究指导了口袋 1 中的螺[5.5]undeca 支架和赖氨酸通道的重要相互作用，并建议延长尾长以提高效力 (IC 50: 高达 399 nM)。所选化合物的细胞增殖试验的有效性能（IC 50：高达 11.9 nM）导致异种移植试验的进一步评估。强效化合物24表现出理想的体内功效，生长抑制率为 77.7%（肿瘤重量减少 4 倍，肿瘤体积减少 3 倍）。此外，通过鉴定主要代谢物（甲硅烷基脱烷基化、可逆水合产物、无毒性醌片段）和充分暴露测试化合物2
• One-Pot Hydrogen Peroxide and Hydrohalic Acid Induced Ring Closure and Selective Aromatic Halogenation To Give New Ring-Fused Benzimidazoles
  作者：Michael Gurry、Martin Sweeney、Patrick McArdle、Fawaz Aldabbagh

  DOI：10.1021/acs.orglett.5b01317

  日期：2015.6.5

  A new series of selectively dichlorinated and dibrominated five- to eight-membered-ring [1,2-a]-fused benzimidazoles and [1,4]oxazino[4,3-a]benzimidazoles are synthesized in mostly high yields of >80% using the reaction of hydrogen peroxide and hydrohalic acid with commercially available o-cyclic amine substituted anilines. Domestic bleach with HCl can also be used for a one-pot ring closure and chlorination

  合成了一系列新的选择性二氯化和二溴化的五至八元环[1,2- a ]稠合的苯并咪唑和[1,4]恶嗪[4,3- a ]苯并咪唑，其大部分收率> 80使用过氧化氢和氢卤酸与可商购的o-环胺取代的苯胺的反应，得到％。含HCl的家用漂白剂也可用于一锅闭环和氯化。
• Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators of caspases and inducers of apoptosis and the use thereof
  申请人：Cytovia, Inc.

  公开号：US20040097503A1

  公开（公告）日：2004-05-20

  The present invention is directed to substituted 2-aryl-4-arylaminopyrimidine and analogs thereof, represented by the general Formula I: 1 wherein A, Ar 1 , Ar 2 , R 1 and R 3 are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. The compounds of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

  本发明涉及取代的2-芳基-4-芳氨基嘧啶及其类似物，由通式I表示：其中A、Ar1、Ar2、R1和R3如本文所定义。本发明还涉及发现具有I式化合物的活化剂和凋亡诱导剂。本发明的化合物可用于在各种临床情况下诱导细胞死亡，其中出现了不受控制的异常细胞的生长和扩散。
• Discovery of substituted 4-anilino-2-arylpyrimidines as a new series of apoptosis inducers using a cell- and caspase-based high throughput screening assay. 2. Structure–activity relationships of the 2-aryl group
  作者：Nilantha Sirisoma、Azra Pervin、Bao Nguyen、Candace Crogan-Grundy、Shailaja Kasibhatla、Ben Tseng、John Drewe、Sui Xiong Cai

  DOI：10.1016/j.bmcl.2009.02.074

  日期：2009.4

  As a continuation of our efforts to discover and develop the apoptosis inducing 4-anilino-2-(2-pyridyl) pyrimidines as potential anticancer agents, we explored replacing the 2-pyridyl group by other aryl groups. SAR studies showed that the 2-pyridyl group can be replaced by a 3-pyridyl, 4-pyridyl and 2-pyrazinyl group, and that the SAR for the anilino group was similar to that of the 2-pyridyl series. However, replacement of the 2-pyridyl group by a phenyl group, a 3,5-dichloro-4-pyridyl group, or a saturated ring led to inactive compounds. Several potent compounds, including 2f, 3d, 3j and 4a, with EC50 values of 0.048-0.024 mu M in the apoptosis induction assay against T47D cells, were identified through the SAR studies. In a tubulin polymerization assay, compound 2f, which was active against all the three cell lines tested (T47D, HTC116 and SNU398), inhibited tubulin polymerization with an IC50 value of 0.5 mu M, while compound 2a, which was active against T47D cells but not active against HTC116 and SNU398 cells, was not active in the tubulin assay at up to 50 mu M. (c) 2009 Elsevier Ltd. All rights reserved.