4-(1-甲基-1H-吡唑-5-基)苯甲酸甲酯 | 179057-12-6

• 物质功能分类: 有机原料 - 烃类化合物及其衍生物 - 芳香烃
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(1-甲基-1H-吡唑-5-基)苯甲酸甲酯
• 英文名称: methyl 4-(1-methyl-1H-pyrazol-5-yl)benzoate
• 英文别名: methyl 4-(1-methylpyrazol-5-yl)benzoate；methyl 4-(2-methylpyrazol-3-yl)benzoate
• CAS: 179057-12-6
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: PYEWEFGLTSTRFG-UHFFFAOYSA-N

物化性质

• 沸点：
  357.5±25.0 °C(Predicted)
• 密度：
  1.16

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  4-(1-甲基-1H-吡唑-5-基)苯甲酸甲酯 在 N-氯代丁二酰亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  作为新型Akt激酶抑制剂的吡唑-呋喃羧酰胺类似物的设计，合成和生物学评估

  摘要：

  设计，合成了一系列新颖的吡唑-呋喃羧酰胺类似物，并对它们的Akt1抑制活性以及针对HCT116和OVCAR-8细胞系的抗增殖功效进行了生物学评估。大多数化合物显示出中等至出色的Akt1抑制活性，以及​​良好的细胞毒性。对最有前途的化合物25e的进一步激酶选择性分析表明，它对结构相关的AGC激酶（包括Akt2，Akt3，ROCK1和PKA）也很有效，但对其他亚家族的激酶具有特异性。另外，蛋白质印迹分析表明25e可以显着抑制PC-3细胞中Akt底物GSK3β的磷酸化水平。而且25e证实LNCaP细胞中PRAS40磷酸化的浓度依赖性抑制，IC 50值为30.4 nM。

  DOI：

  10.1016/j.ejmech.2016.03.074
• 作为产物：
  描述：

  4-乙酰基苯甲酸乙酯 在 溶剂黄146 作用下， 反应 21.0h， 生成 4-(1-甲基-1H-吡唑-5-基)苯甲酸甲酯
  参考文献：
  名称：

  酰基辅酶A的抑制剂：胆固醇O-酰基转移酶。2.新系列的N-烷基-N-（杂芳基取代的苄基）-N'-芳基脲的鉴定和结构-活性关系。

  摘要：

  制备了一系列N-烷基-N-（杂芳基取代的苄基）-N'-芳基脲和相关的衍生物（用2和3表示），并对其在体外和体外抑制酰基辅酶A：胆固醇O-酰基转移酶的能力进行了评估。降低体内胆固醇喂养大鼠的血浆胆固醇水平。在这些新型化合物中，3型系列更为出色。该三取代脲的N-苄基上的吡唑-3-基（即3，Ar1 =吡唑-3-基）被鉴定为杂芳环，提供了良好的生物活性。通过优化与N-烷基（R）和N-芳基（Ar3）的组合的结果，化合物3aq（FR186054）被确定为一种新型的口服有效ACAT抑制剂，在胆固醇喂养的大鼠中表现出有效的体外ACAT抑制活性（兔子肠道微粒体IC50 = 99 nM）和出色的降胆固醇作用，而与给药方式无关（ED50 = 0.046 mg / kg，通过饮食给药，ED50 = 0. 44 mg /通过在PEG400载体中的管饲法施用1kg）。此外，一项毒理学研究表明，以10 mg / kg

  DOI：

  10.1021/jm9800853

文献信息

• Pd-Catalysed Direct 5-Arylation of 1-Methylpyrazole with Aryl Bromides
  作者：Hamed Ammar、Henri Doucet、Anissa Beladhria、Kassem Beydoun、Ridha Salem

  DOI：10.1055/s-0030-1260076

  日期：2011.8

  the base and DMAc as the solvent, promotes the 5-arylation in moderate to high selectivities and yields. A wide variety of aryl and heteroaryl bromide derivatives have been successfully employed. Their electronic and steric properties also have an influence on the regioselectivities and yields of the coupling products. Both electron-poor and electron-rich aryl bromides gave satisfactory results, although

  发现1-甲基吡唑是通过使用芳基溴化物的CH活化/官能化来钯催化的直接芳基化的合适伴侣。发现反应条件和催化剂的性质对选择性具有决定性的影响。使用过量的吡唑（4当量），仅使用0.5-1 mol％的乙酸钯（II）作为催化剂，使用乙酸钾作为碱，并使用DMAc作为溶剂，可在中等至高选择性下促进5-芳基化，产量。已经成功地使用了各种各样的芳基和杂芳基溴化物衍生物。它们的电子和空间特性也影响偶联产物的区域选择性和产率。贫电子和富电子芳基溴化物均获得令人满意的结果，尽管， 芳基化-偶联-钯-吡唑-区域选择性
• Substituted nitrogen-containing heterocyclic derivatives, pharmaceutical compositions comprising the same and applications of antitumor thereof
  申请人：ZHEJIANG UNIVERSITY

  公开号：US10233180B2

  公开（公告）日：2019-03-19

  Disclosed are new substituted nitrogen-containing heterocyclic derivatives represented by formula (I) as AKT inhibitors, optical isomers, pharmaceutically acceptable salts or solvates thereof, wherein the definition of R1, R2, R3, R4, R5, R6, ring A, ring C, B, Q, Y, Z and m is shown in the description for details. In addition, medicaments comprising the derivatives as active components are also disclosed, which can be useful for treating proliferative diseases, such as cancer and inflammation, especially diseases relating to AKT kinase.

  本发明公开了式(I)代表的作为AKT抑制剂的新取代含氮杂环衍生物、其光学异构体、药学上可接受的盐或溶液，其中R1、R2、R3、R4、R5、R6、环A、环C、B、Q、Y、Z和m的定义详见说明。此外，还公开了包含这些衍生物作为活性成分的药物，可用于治疗增殖性疾病，如癌症和炎症，尤其是与 AKT 激酶有关的疾病。
• Discovery of 3,4,6-Trisubstituted Piperidine Derivatives as Orally Active, Low hERG Blocking Akt Inhibitors via Conformational Restriction and Structure-Based Design
  作者：Xiaowu Dong、Wenhu Zhan、Mengting Zhao、Jinxin Che、Xiaoyang Dai、Yizhe Wu、Lei Xu、Yubo Zhou、Yanmei Zhao、Tian Tian、Gang Cheng、Zegao Jin、Jia Li、Yanfei Shao、Qiaojun He、Bo Yang、Qinjie Weng、Yongzhou Hu

  DOI：10.1021/acs.jmedchem.9b00891

  日期：2019.8.8

  A series of 3,4-disubstituted piperidine derivatives were obtained based on a conformational restriction strategy and a lead compound, Al2, that exhibited potent in vitro and in vivo antitumor efficacies; however, obvious safety issues limited its further development. Thus, systematic exploration of the structure activity relationship of compound Al2, involving the phenyl group, hinge-linkage, and piperidine moiety, led to the discovery of the superior 3,4,6-trisubstituted piperidine derivative E22. E22 showed increased potency in Aktl and cancer cell inhibition, remarkably reduced human ether-a-go-go-related gene blockage, and significantly improved safety profiles. Compound E22 also exhibited good kinase selectivity, had a good pharmacokinetic profile, and displayed very potent in vivo antitumor efficacy, with over 90% tumor growth inhibition in the SKOV3 xenograft model. Further mechanistic studies were conducted to demonstrate that compound E22 could significantly inhibit the phosphorylation of proteins downstream of Akt kinase in cells and tumor tissue from the xenograft model.
• SUBSTITUTED NITROGEN-CONTAINING HETEROCYCLIC DERIVATIVES, PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME AND APPLICATIONS OF ANTITUMOR THEREOF
  申请人：Zhejiang University

  公开号：EP3124486B1

  公开（公告）日：2020-12-09
• Phenotypic Screening-Based Identification of 3,4-Disubstituted Piperidine Derivatives as Macrophage M2 Polarization Modulators: An Opportunity for Treating Multiple Sclerosis
  作者：Qinjie Weng、Jinxin Che、Zhikang Zhang、Jiahuan Zheng、Wenhu Zhan、Sendong Lin、Tian Tian、Jincheng Wang、Renhua Gai、Yongzhou Hu、Bo Yang、Qiaojun He、Xiaowu Dong

  DOI：10.1021/acs.jmedchem.8b01635

  日期：2019.4.11

  Multiple sclerosis (MS) is a disease of the autoimmune-mediated disorder in the central nervous system, for which no effective therapeutic agent is currently available. The regulation of macrophage polarization toward M2 is a general benefit for treating MS. The gene biomarker-based phenotypic screening approach was developed, and 3,4-disubstituted piperidine derivative S-28 was identified as a lead compound modulating macrophage M2 polarization. Further SAR studies resulted in the discovery of the most potent modulator D11 that showed good oral bioavailability and significant in vivo therapeutic effects. Mechanistic studies demonstrated that the M2 polarization macrophages modulated by D11 mainly functioned through inhibiting the proliferation of T-cells and activating the phosphorylation of Stat3 and Akt. Therefore, the gene biomarker-based phenotypic screening was demonstrated as a promising tool for the discovery of novel macrophage M2 polarization modulators. Compound D11 may serve as a promising starting point for the development of therapeutics to treat MS.