5-(3,4-二甲氧基苯基)-2H-吡唑-3-胺 | 208519-08-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-(3,4-二甲氧基苯基)-2H-吡唑-3-胺
• 中文别名: 3-(3,4-二甲氧苯基)-1H-吡唑-5-胺
• 英文名称: 3-(3,4-dimethoxyphenyl)-1H-pyrazol-5-amine
• 英文别名: 5-(3,4-dimethoxyphenyl)-1H-pyrazol-3-amine
• CAS: 208519-08-8
• 化学式: C₁₁H₁₃N₃O₂
• mdl: MFCD02664228
• 分子量: 219.243
• InChiKey: UKCBIFQXFFDGHC-UHFFFAOYSA-N

物化性质

• 熔点：
  131-133°C
• 沸点：
  463.9±45.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  73.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi

反应信息

• 作为反应物：
  描述：

  5-(3,4-二甲氧基苯基)-2H-吡唑-3-胺 在 aluminum (III) chloride 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 3-(3,4-dimethoxyphenyl)-5-(p-tolyl)-1H-pyrazolo[3,4-b]pyridine
  参考文献：
  名称：

  3,5-二芳基-1 H-吡唑并[3,4- b ]吡啶类作为有效的微管蛋白聚合抑制剂：合理的设计，合成和生物学评估

  摘要：

  通过环系策略设计了一系列新型的3,5-二芳基-1 H-吡唑并[3,4- b ]吡啶类化合物作为针对秋水仙碱位点的微管蛋白聚合抑制剂，并得到了构象分析的支持。一般的化学上不稳定的旋转接头碳原子团被1 H-吡唑并[3,4- b ]吡啶锁定，以避免羰基还原并限制由碳-碳单键旋转引起的分子构象的不稳定性羰基。合成了所有目标化合物，并通过MTT分析评估了其对三种人类癌症细胞系（SGC-7901，A549和HeLa）的抗增殖活性。这些化合物大多数显示出突出的体外效力和该支架13d中最有效的化合物（SGC-7901：IC 50  = 13 nM）可以显着抑制微管蛋白聚合并强烈破坏细胞骨架。分子建模研究的结果表明，13d通过与秋水仙碱位点结合而与微管蛋白相互作用。

  DOI：

  10.1016/j.ejmech.2018.12.053
• 作为产物：
  描述：

  3,4-二甲氧基苯甲酸甲酯 在 sodium hydride 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 11.0h， 生成 5-(3,4-二甲氧基苯基)-2H-吡唑-3-胺
  参考文献：
  名称：

  Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model

  摘要：

  FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV411 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.05.021

文献信息

• Design, synthesis, and evaluation of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines as novel PDE-4 inhibitors
  作者：Ikyon Kim、Jong Hwan Song、Chang Min Park、Joon Won Jeong、Hyung Rae Kim、Jin Ryul Ha、Zaesung No、Young-Lan Hyun、Young Sik Cho、Nam Sook Kang、Dong Ju Jeon

  DOI：10.1016/j.bmcl.2009.12.070

  日期：2010.2

  is design, synthesis, and biological evaluation of novel series of 2-aryl-7-(3′,4′-dialkoxyphenyl)-pyrazolo[1,5-a]pyrimidines acting as inhibitors of type 4 phosphodiesterase (PDE4) which is known as a good target for the treatment of asthma and COPD. For this purpose, structure optimization was conducted with the aid of structure-based drug design using the known X-ray crystallography. Also, biological

  本文描述了新颖的2-芳基-7-（3'，4'-二烷氧基苯基）-吡唑并[1,5- a ]嘧啶系列的新颖系列的设计，合成和生物学评估，该抑制剂可作为4型磷酸二酯酶（PDE4）的抑制剂被认为是治疗哮喘和COPD的好靶标。为此目的，使用已知的X射线晶体学，借助于基于结构的药物设计进行结构优化。此外，通过使用体外测定法评估了这些化合物对目标酶的生物学作用，从而产生了有效且选择性的PDE-4抑制剂（IC 50  <10 nM）。
• TRK INHIBITION
  申请人：NantBio, Inc.

  公开号：US20180346451A1

  公开（公告）日：2018-12-06

  The present invention relates to the use of substituted pyrimidine derivatives to modulate tropomyosin-related kinase (Trk) family protein kinase, and the use of the substituted pyrimidine derivatives for the treatment of pain, inflammation, cancer, restenosis, atherosclerosis, psoriasis, thrombosis, a disease, disorder, injury, or malfunction relating to dysmyelination or demyelination or a disease or disorder associated with abnormal activities of nerve growth factor (NGF) receptor TrkA.

  本发明涉及使用取代嘧啶衍生物来调节肌球蛋白相关激酶（Trk）家族蛋白激酶，并且使用这些取代嘧啶衍生物来治疗疼痛、炎症、癌症、再狭窄、动脉粥样硬化、牛皮癣、血栓形成、与失髓鞘或脱髓鞘相关的疾病、紊乱、损伤或功能障碍，或与神经生长因子（NGF）受体TrkA异常活动相关的疾病或紊乱。
• Urea derivatives
  申请人：Banyu Pharmaceutical Co., Ltd.

  公开号：US06043246A1

  公开（公告）日：2000-03-28

  The present invention relates to a compound represented by the general formula [I]: ##STR1## wherein A represents a nitrogen atom or a group represented by C--R.sup.5 ; Ar.sup.1 represents an aryl group which may have a substituent selected from the group consisting of a halogen atom and lower alkyl and lower haloalkyl groups; Ar.sup.2 represents an aryl or heteroaryl group which may have a substituent selected from the group consisting of a halogen atom and lower alkyl, lower alkenyl, lower haloalkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower dialkylamino and aryl groups; R.sup.1 represents a hydrogen atom, a lower alkyl group or a bond formed by linking to R.sup.5 ; R.sup.2 represents a hydrogen atom or a lower alkyl group; R.sup.3 and R.sup.4 may be the same or different and each represents a hydrogen atom or a lower alkyl group, or R.sup.3 and R.sup.4 are linked to each other to form an alkylene group containing 2 to 4 carbon atoms which may have a lower alkyl group; and R.sup.5 represents a hydrogen atom or a hydroxyl, lower alkyl or lower alkoxy group or a bond formed by linking to R.sup.1, or its salt, a process for its preparation and an agent for the treatment of bulimia, obesity or diabetes comprising it as an active ingredient.

  本发明涉及一种由通式[I]表示的化合物：##STR1## 其中A代表氮原子或由C-R.sup.5表示的基团; Ar.sup.1代表芳基基团，可以具有从卤原子和较低的烷基和卤代烷基组成的取代基; Ar.sup.2代表芳基或杂环芳基，可以具有从卤原子和较低的烷基，较低的烯基，较低的卤代烷基，较低的烷氧基，较低的烷硫基，较低的烷基氨基，较低的二烷基氨基和芳基组成的取代基; R.sup.1代表氢原子，较低的烷基或通过与R.sup.5连接形成的键; R.sup.2代表氢原子或较低的烷基; R.sup.3和R.sup.4可以相同也可以不同，每个代表氢原子或较低的烷基，或R.sup.3和R.sup.4连接在一起形成含有2到4个碳原子的烷基，可以具有较低的烷基; R.sup.5代表氢原子或羟基，较低的烷基或较低的烷氧基，或通过与R.sup.1连接形成的键，或其盐，其制备方法以及作为活性成分的治疗暴食症、肥胖症或糖尿病的药剂。
• Design and synthesis of novel 3-amino-5-phenylpyrazole derivatives as tubulin polymerization inhibitors targeting the colchicine-binding site
  作者：Yang Yang、Yan Cao、Jingwen Yu、Xinyu Yu、Yali Guo、Fei Wang、Qingjia Ren、Caolong Li

  DOI：10.1016/j.ejmech.2024.116177

  日期：2024.3

  5b can inhibit the polymerization of tubulin targeting the tubulin colchicine-binding sites. Furthermore, 5b could arrest MCF-7 cells at the G2/M phase and induce MCF-7 cells apoptotic in a dose-dependent and time-dependent manners, and regulate the level of related proteins expression. Besides, compound 5b could inhibit the cancer cell migration and angiogenesis. In addition, 5b could inhibit tumor

  微管蛋白作为微管的基本单位，是抗癌物研究中最重要的靶点之一。设计合成了一系列新颖的 3-氨基-5-苯基吡唑衍生物，并评价了它们的生物活性。其中，大多数化合物在体外对 5 种癌细胞系发挥了优异的抑制活性。特别是化合物 5b 对 MCF-7 细胞表现出很强的抗增殖活性，IC50 值为 38.37 nM。进一步的研究表明，化合物 5b 可以抑制靶向微管蛋白秋水仙碱结合位点的微管蛋白聚合。此外，5b 可以阻滞 MCF-7 细胞在 G2/M 期，并以剂量依赖性和时间依赖性方式诱导 MCF-7 细胞凋亡，并调节相关蛋白的表达水平。此外，化合物 5b 可以抑制癌细胞迁移和血管生成。此外，5b 可以抑制 MCF-7 异种移植模型中的肿瘤生长，无明显毒性。所有这些结果表明，5b 可能是一种很有前途的靶向微管蛋白秋水仙碱结合位点的抗肿瘤药物，值得进一步研究。
• PYRAZOLE DERIVATIVES
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP0945438A1

  公开（公告）日：1999-09-29

  The present invention relates to a compound represented by the general formula [I]: wherein A and B rings are ortho-condensed to each other, A ring represents an aromatic carbocyclic or heterocyclic ring and B ring represents an aliphatic four- to seven-membered carbocyclic or nitrogen-containing heterocyclic ring, said nitrogen atom being possible to present at only the position where the A ring is condensed; Ar represents an aromatic carbocyclic or heterocyclic ring group which may have a substituent selected from the group consisting of a halogen atom and lower alkyl, lower alkenyl, lower haloalkyl, lower alkoxy, lower alkylthio, lower alkylamino, lower dialkylamino and aromatic carbocyclic ring groups; and R represents a substituent selected from the group consisting of a halogen atom and nitro, lower alkyl, lower alkoxy, aromatic carbocyclic ring groups and a carbonyl group having an aromatic carbocyclic ring group, or a hydrogen atom, provided that when the group represented by is the group represented by Ar is not a phenyl group nor a 4-chlorophenyl group, or its salt, a method for its preparation as well as an agent for the treatment of bulimia, obesity or diabetes comprising it as an active ingredient.

  本发明涉及通式[I]代表的化合物： 其中 A 环和 B 环彼此正交缩合，A 环代表芳香族碳环或杂环，B 环代表脂肪族四至七元碳环或含氮杂环，所述氮原子可能仅存在于 A 环缩合的位置；Ar 代表芳香碳环或杂环基团，其取代基可选自由卤素原子、低级烷基、低级烯基、低级卤代烷基、低级烷氧基、低级烷硫基、低级烷氨基、低级二烷基氨基和芳香碳环基团组成的组；和 R 代表选自卤素原子和硝基、低级烷基、低级烷氧基、芳香族碳环基团和具有芳香族碳环基团的羰基或氢原子的取代基，条件是当由 代表的基团 Ar 不是苯基，也不是 4-氯苯基、 或其盐，其制备方法以及治疗暴食症、肥胖症或糖尿病的药物，其活性成分均包含该物质。