3-叔丁基-1-(4-硝基苯基)-1H-吡唑-5-胺 | 251658-55-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 3-叔丁基-1-(4-硝基苯基)-1H-吡唑-5-胺
• 英文名称: 3-(tert-butyl)-1-(4-nitrophenyl)-1H-pyrazol-5-amine
• 英文别名: 5-amino-3-tert-butyl-1-(4-nitrophenyl)-1H-pyrazole；3-tert-butyl-1-(4-nitrophenyl)-1H-pyrazol-5-amine；5-tert-butyl-2-(4-nitrophenyl)pyrazol-3-amine
• CAS: 251658-55-6
• 化学式: C₁₃H₁₆N₄O₂
• mdl: MFCD04115074
• 分子量: 260.296
• InChiKey: WVQSWOBETMRYCD-UHFFFAOYSA-N

物化性质

• 熔点：
  164-167°C

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.307
• 拓扑面积：
  89.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  3-叔丁基-1-(4-硝基苯基)-1H-吡唑-5-胺 在 palladium on activated charcoal 吡啶 、 ammonium formate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 生成 N-(4-{3-tert-butyl-5-[({4-[2-(morpholin-4-yl)ethoxy]naphthalen-1-yl}carbamoyl)amino]-1H-pyrazol-1-yl}phenyl)acetamide
  参考文献：
  名称：

  Structure−Activity Relationships of the p38α MAP Kinase Inhibitor 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naph- thalen-1-yl]urea (BIRB 796)

  摘要：

  We report on the structure-activity relationships (SAR) of 1-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]urea (BIRB 796), an inhibitor of p38alpha MAP kinase which has advanced into human clinical trials for the treatment of autoimmune diseases. Thermal denaturation was used to establish molecular binding affinities for this class of p38alpha inhibitors. The tert-butyl group remains a critical binding element by occupying a lipophilic domain in the kinase which is exposed upon rearrangement of the activation loop. An aromatic ring attached to N-2 of the pyrazole nucleus provides important pi-CH2 interactions with the kinase. The role of groups attached through an ethoxy group to the 4-position of the naphthalene and directed into the ATP-binding domain is elucidated. Pharmacophores with good hydrogen bonding potential, such as morpholine, pyridine, and imidazole, shift the melting temperature of p38alpha by 16-17 degreesC translating into K-d values of 50-100 pM. Finally, we describe several compounds that potently inhibit TNF-alpha production when dosed orally in mice.

  DOI：

  10.1021/jm030121k
• 作为产物：
  描述：

  新戊酰基乙腈 、 4-硝基苯肼盐酸盐 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 8.0h， 生成 3-叔丁基-1-(4-硝基苯基)-1H-吡唑-5-胺
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of Novel Substituted N,N′-Diaryl ureas as Potent p38 Inhibitors

  摘要：

  基于p38α MAPK与其他激酶相比具有两个关键残基（Gly110和Thr106）差异，设计并合成了一系列作为p38α抑制剂的替代N,N′-二芳基脲类化合物。初步生物学评估表明，大多数化合物具有良好的p38α抑制活性。在这些化合物中，9g似乎是最强大的，并且是我们未来研究的主要化合物。

  DOI：

  10.3390/molecules200916604

文献信息

• Synthesis and Biological Evaluation of Chromenylurea and Chromanylurea Derivatives as Anti-TNF-α agents that Target the p38 MAPK Pathway
  作者：Xingzhou Li、Xinming Zhou、Jing Zhang、Lili Wang、Long Long、Zhibing Zheng、Song Li、Wu Zhong

  DOI：10.3390/molecules19022004

  日期：——

  A series of 1-aryl-3-(2H-chromen-5-yl)urea and 1-aryl-3-(chroman-5-yl)urea derivatives were designed, synthesized and evaluated for their inhibitory activities towards TNF-α production in lipopolysaccharide-stimulated THP-1 cells. The most active compound, 40g, inhibited TNF-α release with an IC50 value of 0.033 μM, which is equipotent to that of BIRB796 (IC50 = 0.032 μM).

  设计、合成并评估了一系列1-芳基-3-(2H-色烯-5-基)脲和1-芳基-3-(色满-5-基)脲衍生物对脂多糖刺激的THP-1细胞中TNF-α产生抑制活性。活性最高的化合物40g能以0.033 μM的IC50值抑制TNF-α的释放，与BIRB796的效力相当（IC50 = 0.032 μM）。
• Synthesis and p38 Inhibitory Activity of Some Novel Substituted N,N′-Diarylurea Derivatives
  作者：Dianxi Zhu、Qifeng Xing、Ruiyuan Cao、Dongmei Zhao、Wu Zhong

  DOI：10.3390/molecules21050677

  日期：——

  We have identified a novel series of substituted N,N'-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 × 10(-8) and appears to be the

  我们已经鉴定出一系列新的取代的N，N'-二芳基脲p38α抑制剂。测试了目标化合物对BHK细胞中p38α，MAPKAPK2酶的抑制活性，LPS刺激的THP-1细胞中TNF-α的释放以及p38α结合实验。在这些化合物中，25a抑制p38α酶的IC50值为0.47 nM，KD值为1.54×10（-8），似乎是该系列中最有希望的化合物。
• Short Synthesis of 1-(3-<i>tert</i>-Butyl-1-phenyl-1<i>H</i>-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2<i>H</i>-chromen-8-yl) Urea Derivatives
  作者：Xingzhou Li、Xinming Zhou、Zhibing Zheng、Wu Zhong、Junhai Xiao、Song Li

  DOI：10.1080/00397910902883603

  日期：2009.10.21

  efficient synthesis of 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2H-chromen-8-yl) urea derivatives (1a–c), a novel type of p38 MAPK inhibitors, is described. The Claisen thermal rearrangement of arylpropargyl ethers was employd as a key step to synthesize the chromene core. The solvent effect on the ratio of the resultant two isomers of Claisen thermal rearrangement, namely 2-methylbenzofuran

  摘要 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2H-chromen-8-yl) 尿素衍生物的快速高效合成(1a-c) 是一种新型的 p38 MAPK 抑制剂。芳基炔丙基醚的克莱森热重排被用作合成色烯核心的关键步骤。还研究了溶剂对克莱森热重排的所得两种异构体，即 2-甲基苯并呋喃和 2H-色烯的比例的影响。
• Design, Synthesis and Biological Evaluation of Novel Substituted N,N′-Diaryl ureas as Potent p38 Inhibitors
  作者：Dianxi Zhu、Xingzhou Li、Wu Zhong、Dongmei Zhao

  DOI：10.3390/molecules200916604

  日期：——

  A novel series of substituted N,N′-diaryl ureas that act as p38α inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38α MAPK than in other kinases. Preliminary biological evaluation indicated that most compounds possessed good p38α inhibitory potencies. Among these compounds, 9g appeared to be the most powerful and is the main compound that we will study in the future.

  基于p38α MAPK与其他激酶相比具有两个关键残基（Gly110和Thr106）差异，设计并合成了一系列作为p38α抑制剂的替代N,N′-二芳基脲类化合物。初步生物学评估表明，大多数化合物具有良好的p38α抑制活性。在这些化合物中，9g似乎是最强大的，并且是我们未来研究的主要化合物。
• Substituted 1-(4-aminophenyl)pyrazoles and their use as anti-inflammatory agents
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US06506747B1

  公开（公告）日：2003-01-14

  1-(4-aminophenyl)pyrazoles optionally substituted on the 3- and 5-positions of the pyrazole ring and on the amino group at the 4-position of the phenyl ring are disclosed and described, which pyrazoles inhibit IL-2 production in T-lymphocytes.

  所述的1-(4-氨基苯基)吡唑可以选择地在吡唑环的3-和5-位置以及苯环的4-位置上取代氨基团，并且这些吡唑抑制T淋巴细胞中的IL-2产生。