5-amino-N-(4-fluorophenyl)-1H-pyrazole-4-carboxamide | 1106749-29-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-amino-N-(4-fluorophenyl)-1H-pyrazole-4-carboxamide
• CAS: 1106749-29-4
• 化学式: C₁₀H₉FN₄O
• mdl: MFCD11108769
• 分子量: 220.206
• InChiKey: VFROZRVTHUQNPW-UHFFFAOYSA-N

物化性质

• 沸点：
  368.3±37.0 °C(Predicted)
• 密度：
  1.504±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[4-cyano-phenylcarbamoyl]-acetic acid 、 5-amino-N-(4-fluorophenyl)-1H-pyrazole-4-carboxamide 以 溶剂黄146 为溶剂， 反应 1.0h， 生成 5-(4-cyanobenzyl)-N-(4-fluorophenyl)-7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxamide
  参考文献：
  名称：

  Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design

  摘要：

  Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug design and co-crystal structures with Pim-1 kinase to guide analog design, we were able to improve potency against all three Pim isoforms including a significant 10,000-fold gain against Pim-2. Compound 17 is a novel lead with low picomolar potency on all three Pim kinase isoforms. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.020
• 作为产物：
  描述：

  benzyl (4-((4-fluorophenyl)carbamoyl)-1H-pyrazol-5-yl)carbamate 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 生成 5-amino-N-(4-fluorophenyl)-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Discovery of novel pyrazolo[1,5-a]pyrimidines as potent pan-Pim inhibitors by structure- and property-based drug design

  摘要：

  Pim kinases are promising targets for the development of cancer therapeutics. Among the three Pim isoforms, Pim-2 is particularly important in multiple myeloma, yet is the most difficult to inhibit due to its high affinity for ATP. We identified compound 1 via high throughput screening. Using property-based drug design and co-crystal structures with Pim-1 kinase to guide analog design, we were able to improve potency against all three Pim isoforms including a significant 10,000-fold gain against Pim-2. Compound 17 is a novel lead with low picomolar potency on all three Pim kinase isoforms. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.020

文献信息

• Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2-<i>b</i> ]pyrazole-7-carboxamides
  作者：András Demjén、Róbert Alföldi、Anikó Angyal、Márió Gyuris、László Hackler、Gábor J. Szebeni、János Wölfling、László G. Puskás、Iván Kanizsai

  DOI：10.1002/ardp.201800062

  日期：2018.7

  The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2‐b]pyrazole‐7‐carboxamides were investigated. Following a hit‐to‐lead optimization exploiting 2D and 3D cultures of MCF‐7 human breast, 4T1 mammary gland, and HL‐60 human promyelocytic leukemia cancer cell lines, a 67‐membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized

  研究了新型咪唑并[1,2-b]吡唑-7-甲酰胺的合成和体外细胞毒特性。在利用 MCF-7 人乳腺、4T1 乳腺和 HL-60 人早幼粒细胞白血病癌细胞系的 2D 和 3D 培养物进行先导优化后，构建了一个 67 元文库，并构建了构效关系（SAR ) 确定。七个合成的类似物表现出亚微摩尔活性，其中化合物 63 发挥最显着的效力，具有显着的 HL-60 敏感性（IC50 = 0.183 μM）。
• New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized
  作者：Maryna V Murlykina、Maryna N Kornet、Sergey M Desenko、Svetlana V Shishkina、Oleg V Shishkin、Aleksander A Brazhko、Vladimir I Musatov、Erik V Van der Eycken、Valentin A Chebanov

  DOI：10.3762/bjoc.13.104

  日期：——

  novel features of a Groebke-Blackburn-Bienaymé cyclocondensation are established and discussed. The heterocycles obtained were evaluated for their antibacterial activity and several of them demonstrated a weak antimicrobial effect, but for most of the compounds a 30-50% increase in biomass of Gram-positive strains (mainly B. subtilis) compared to control was observed.

  在 Ugi 和 Groebke-Blackburn-Bienaymé 多组分反应中，对著名的氨基唑、3-氨基-5-甲基异恶唑和 5-氨基-N-芳基-1H-吡唑-4-甲酰胺作为胺组分进行了研究。发现了氨基唑在 Ugi 四组分反应中应用的第一个例子，并建立并讨论了 Groebke-Blackburn-Bienaymé 环缩合的新特征。对获得的杂环化合物的抗菌活性进行了评估，其中一些化合物显示出较弱的抗菌作用，但对于大多数化合物而言，观察到与对照相比，革兰氏阳性菌株（主要是枯草芽孢杆菌）的生物量增加了 30-50%。
• [EN] IMIDAZO-PYRAZOLE CARBOXAMIDE DERIVATIVES AS ANTICANCER AGENTS AND THE SYNTHESIS THEREOF<br/>[FR] DÉRIVÉS D'IMIDAZO-PYRAZOLE CARBOXAMIDE UTILISÉS EN TANT QU'AGENTS ANTICANCÉREUX ET LEUR SYNTHÈSE
  申请人：AVIDIN KFT

  公开号：WO2019220155A1

  公开（公告）日：2019-11-21

  The present invention relates to novel imidazo[1,2-b]pyrazole carboxamide and carbothioamide derivatives of general formula (V), and the advantageous derivatives and pharmaceutically acceptable salts thereof, the synthesis thereof, and medicinal and/or pharmaceutical composition comprising these compounds thereof and synthesis thereof, and for use as a medicament, for use in the treatment of different diseases, advantageously of cancer. The subject compounds are advantageously for use in the treatment of solid malignancies, advantageously breast, lung, melanoma, gliomas, and myeloproliferative and myelodysplastic neoplasms, acute myelogenous/myeloid leukemias and colon cancer by the differentiation and subsequent apoptosis of pre-matured myeloid leukemic cells or myeloid-derived suppressor cells and/or by direct effect on solid tumors.

  本发明涉及一种新型咪唑并[1,2-b]吡唑酮和巯基酮衍生物，其通式为(V)，以及有益的衍生物和其药用可接受的盐，其合成，以及包含这些化合物的药用和/或制药组合物，以及用作药物，用于治疗不同疾病，尤其是癌症。所述化合物有益地用于治疗实体恶性肿瘤，尤其是乳腺癌、肺癌、黑色素瘤、胶质瘤、骨髓增生性和骨髓增生异常新生物、急性髓细胞白血病和结肠癌，通过促使早期髓细胞白血病细胞或髓源性抑制细胞分化和随后凋亡，和/或通过对实体肿瘤的直接作用。
• Imidazo[1,2-b]pyrazole-7-carboxamides Induce Apoptosis in Human Leukemia Cells at Nanomolar Concentrations
  作者：Gábor Szebeni、József Balog、András Demjén、Róbert Alföldi、Vanessza Végi、Liliána Fehér、Imola Mán、Edit Kotogány、Barbara Gubán、Péter Batár、László Hackler、Iván Kanizsai、László Puskás

  DOI：10.3390/molecules23112845

  日期：——

  novel therapeutics. Eight imidazo[1,2-b]pyrazole-7-carboxamides have been tested for cytotoxic activity against five leukemia cell lines: Acute promyelocytic leukemia (HL-60), acute monocytic leukemia (THP-1), acute T-lymphoblastic leukemia (MOLT-4), biphenotypic B myelomonocytic leukemia (MV-4-11), and erythroleukemia (K-562) cells in vitro. Imidazo[1,2-b]pyrazole-7-carboxamides hampered the viability

  白血病，造血系统的恶性肿瘤占成年人总生存率较差的癌症病例的10％。因此，迫切需要开发新的治疗药物。测试了八种咪唑并[1,2-b]吡唑-7-羧酰胺对五种白血病细胞系的细胞毒活性：急性早幼粒细胞白血病（HL-60），急性单核细胞白血病（THP-1），急性T淋巴细胞白血病（ MOLT-4），双表型B骨髓单核细胞白血病（MV-4-11）和红细胞白血病（K-562）细胞。咪唑并[1,2-b]吡唑-7-羧酰胺阻碍了所有五个具有不同潜能的白血病细胞的存活。通过结构活性关系进行的优化得出最有效的前导化合物DU385的以下IC50值：在HL-60，MOLT-4上为16.54 nM，27.24 nM和32.25 nM，MV-4-11细胞，分别。在应用浓度范围内，人类原代成纤维细胞的敏感性要低得多。鼠4T1和人MCF7乳腺癌细胞的单层或球状培养物对1.5×10.8μMIC50值的治疗均较不敏感。流式细胞术证实不