1-phenyl-3-(pyridin-4-yl)-1H-pyrazole-4-carboxylic acid | 957354-76-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-phenyl-3-(pyridin-4-yl)-1H-pyrazole-4-carboxylic acid
• 英文别名: 1-phenyl-3-pyridin-4-ylpyrazole-4-carboxylic acid
• CAS: 957354-76-6
• 化学式: C₁₅H₁₁N₃O₂
• mdl: MFCD05987121
• 分子量: 265.271
• InChiKey: AHZAEZDHBZOUCG-UHFFFAOYSA-N

物化性质

• 沸点：
  461.5±30.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  对羟基联苯 、 1-phenyl-3-(pyridin-4-yl)-1H-pyrazole-4-carboxylic acid 在 氯甲酸乙酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以50%的产率得到1-phenyl-3-(pyridin-4-yl)-1H-pyrazole-4-carboxylic acid biphenyl-4-yl ester
  参考文献：
  名称：

  Synthesis, cytotoxicity, and molecular properties prediction of novel 1,3-diarylpyrazole derivatives

  摘要：

  A novel combinatorial library of ester and amide derivatives of 1,3-diarylpyrazoles was designed and synthesized. Anticancer activities of these compounds were assessed against MCF7, MDA-MB-231, HeLa, Raji, and HL60 human cancer cells by MTT assay. Out of these, compounds 4c and 5f were found as the most promising anticancer agents with IC50 values of 8.12 and 9.63 mu M in Raji cells, respectively. All compounds exhibited suitable drug-like characteristics according to Lipinski's rule.

  DOI：

  10.1007/s00044-013-0505-8
• 作为产物：
  描述：

  4-乙酰吡啶 在 potassium permanganate 、 溶剂黄146 、 potassium hydroxide 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 8.5h， 生成 1-phenyl-3-(pyridin-4-yl)-1H-pyrazole-4-carboxylic acid
  参考文献：
  名称：

  发现吡唑衍生物作为组蛋白赖氨酸特异性脱甲基酶5B（KDM5B / JARID1B）的细胞活性抑制剂

  摘要：

  KDM5B（也称为PLU-1和JARID1B）是2-氧戊二酸和Fe 2+依赖性加氧酶，可作为组蛋白H3K4脱甲基酶，是抑制肿瘤抑制因子（作为药物靶标）表达的关键参与者。在这里，我们介绍了通过基于结构的虚拟筛选和生化筛选发现吡唑衍生物化合物5的效果，针对KDM5B的IC 50为9.320μM，随后对其进行了优化以得到1-（4-甲氧基苯基）-N-（2-甲基- 2-吗啉代丙基）-3-苯基-1H-吡唑-4-羧酰胺（27 ab），一种有效的KDM5B抑制剂，IC 50为0.0244μM 。在MKN45细胞中，化合物27 ab可以结合和稳定KDM5B并诱导H3K4me2 / 3（真正的KDM5B底物）积累，同时保持H3K4me1，H3K9me2 / 3和H3K27me2的含量不变。进一步的生物学研究还表明，化合物27 ab是一种有效的细胞活性KDM5B抑制剂，可以抑制MKN45细胞增殖，伤口愈合和迁移

  DOI：

  10.1016/j.ejmech.2020.112161

文献信息

• Design and Synthesis of Imidazole and Triazole Pyrazoles as <i>Mycobacterium Tuberculosis</i> CYP121A1 Inhibitors
  作者：Safaa M. Kishk、Kirsty J. McLean、Sakshi Sood、Darren Smith、Jack W.D. Evans、Mohamed A. Helal、Mohamed S. Gomaa、Ismail Salama、Samia M. Mostafa、Luiz Pedro S. de Carvalho、Colin W. Levy、Andrew W. Munro、Claire Simons

  DOI：10.1002/open.201900227

  日期：2019.7

  approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity (KD). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl (10 f) and tert‐butyl

  无法治疗的结核分枝杆菌耐药菌株的出现是世界范围内的一个重大公共卫生问题，迫切需要寻找新的有效治疗方法。结核分枝杆菌细胞色素 P450 CYP121A1 由于其在分枝杆菌生长中的重要作用，是治疗结核病的有前途的药物靶点。采用包括分子模型研究在内的合理方法，通过两条合成途径设计了三个系列的唑吡唑衍生物。合成的化合物对结核分枝杆菌的抑制活性及其蛋白质结合亲和力（K D）进行了生物学评估。系列 3 联芳基吡唑咪唑衍生物对异丁基 ( 10 f ) 和叔丁基 ( 10 g ) 化合物最有效，表现出最佳活性（MIC 1.562 μg/mL，K D 0.22 μM ( 10 f ) 和 4.81 μM ( 10 g ) ）。光谱数据表明，所有合成的化合物均产生血红素索雷带的 II 型红移，表明与血红素铁直接结合或（在观察到不太广泛的索雷位移）假定通过间质水分子间接结合。生物和物理化学特性的评估确定了以下活性要求：LogP
• INHIBITOR COMPOUNDS FOR MALE CONTRACEPTION
  申请人：University of Washington

  公开号：US20210332030A1

  公开（公告）日：2021-10-28

  Pyrazole compounds and piperazine compounds that are inhibitors of ALDH1A1 and ALDH1A2 and methods for using the pyrazole compounds and piperazine compounds in male contraceptive compositions for preventing spermatogenesis.
• [EN] PYRAZOLE DERIVATIVES AS MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS<br/>[FR] COMPOSES ET COMPOSITIONS DE MODULATION
  申请人：CAREX SA

  公开号：WO2004043951A1

  公开（公告）日：2004-05-27

  The present invention relates to compounds, compositions and methods useful for modulating nuclear receptors activity in cells, and for treating and/or preventing various diseases and conditions mediated by said nuclear receptors, including metabolic or cell proliferative disorders. According to particular aspects, the present invention relates to compounds, compositions and methods useful for modulating activities of the Peroxisome Proliferator Activated Receptors (PPARs) and for treating and/or preventing various disease and conditions mediated by said nuclear receptors. More specifically, it relates to Peroxigome Proliferator Activated Receptor-gamma (PPAR-gamma) ligands, which are useful in the modulation of blood glucose levels and in the increase of insulin sensitivity in patients in need thereof. The properties of the compounds and compositions of the invention make these PPAR ligands particularly useful in the treatment of those diseases and conditions including diabetes, atherosclerosis, hyperglycemia, dyslipidemia, obesity, syndrome X, insulin resistance, hypertension, neuropathy, microvascular diseases (e.g. retinopathy, nephropathy), macrovascular diseases (e.g. myocardial infarction, stroke, heart failure) in mammals.
• Synthesis, cytotoxicity, and molecular properties prediction of novel 1,3-diarylpyrazole derivatives
  作者：Sultan Nacak Baytas、Nazan Inceler、Akın Yılmaz

  DOI：10.1007/s00044-013-0505-8

  日期：2013.10

  A novel combinatorial library of ester and amide derivatives of 1,3-diarylpyrazoles was designed and synthesized. Anticancer activities of these compounds were assessed against MCF7, MDA-MB-231, HeLa, Raji, and HL60 human cancer cells by MTT assay. Out of these, compounds 4c and 5f were found as the most promising anticancer agents with IC50 values of 8.12 and 9.63 mu M in Raji cells, respectively. All compounds exhibited suitable drug-like characteristics according to Lipinski's rule.
• Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B)
  作者：Bing Zhao、Qianqian Liang、Hongmei Ren、Xinhui Zhang、Yang Wu、Kun Zhang、Li-Ying Ma、Yi-Chao Zheng、Hong-Min Liu

  DOI：10.1016/j.ejmech.2020.112161

  日期：2020.4

  KDM5B (also known as PLU-1 and JARID1B) is 2-oxoglutarate and Fe2+ dependent oxygenase that acts as a histone H3K4 demethylase, which is a key participant in inhibiting the expression of tumor suppressors as a drug target. Here, we present the discovery of pyrazole derivatives compound 5 by structure-based virtual screening and biochemical screening with IC50 of 9.320 μM against KDM5B, and its subsequent

  KDM5B（也称为PLU-1和JARID1B）是2-氧戊二酸和Fe 2+依赖性加氧酶，可作为组蛋白H3K4脱甲基酶，是抑制肿瘤抑制因子（作为药物靶标）表达的关键参与者。在这里，我们介绍了通过基于结构的虚拟筛选和生化筛选发现吡唑衍生物化合物5的效果，针对KDM5B的IC 50为9.320μM，随后对其进行了优化以得到1-（4-甲氧基苯基）-N-（2-甲基- 2-吗啉代丙基）-3-苯基-1H-吡唑-4-羧酰胺（27 ab），一种有效的KDM5B抑制剂，IC 50为0.0244μM 。在MKN45细胞中，化合物27 ab可以结合和稳定KDM5B并诱导H3K4me2 / 3（真正的KDM5B底物）积累，同时保持H3K4me1，H3K9me2 / 3和H3K27me2的含量不变。进一步的生物学研究还表明，化合物27 ab是一种有效的细胞活性KDM5B抑制剂，可以抑制MKN45细胞增殖，伤口愈合和迁移