1-methyl-1H-pyrazole-4-carbonyl isothiocyanate | 1154393-03-9

• 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-methyl-1H-pyrazole-4-carbonyl isothiocyanate
• 英文别名: 1-methylpyrazole-4-carbonyl isothiocyanate
• CAS: 1154393-03-9
• 化学式: C₆H₅N₃OS
• 分子量: 167.191
• InChiKey: VVUPKTYNAAJWEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  79.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-methyl-1H-pyrazole-4-carbonyl isothiocyanate 在 吡啶 、 水 、 氢溴酸 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 N-(3-(4-bromophenyl)-4-methylthiazol-2(3H)-ylidene)-1-methyl-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Synthesis and apoptotic activity of new pyrazole derivatives in cancer cell lines

  摘要：

  We designed and synthesized new pyrazole thiourea chimeric derivatives and confirmed their structures by NMR and IR spectra. Apoptotic effects were studied in human cancer cells. The N-[(1-methyl-1H-pyrazol-4-yl)carbonyl]-N'-(3-bromophenyl)-thiourea compound (4b) exhibited the highest apoptosis-inducing effect. Compound 4b and the thiazole derivatives, 5b and 6b, increased the expression of tumor necrosis factor receptors TRAIL-R2 and TRAIL-R1, accompanied by down-modulation of pro-caspase 3 levels, and the augmentation of cleaved caspase 3. They also reduced the levels of apoptosis inhibitory proteins and the expression of the heat-shock proteins Hsp27 and Hsp70. All the tested pyrazole derivatives induced a concentration-dependent increase of cells in G2/M phases. The analysis of the experimental data indicates the reduction of Akt phosphorylation as the most probable cellular mechanism of action for the tested compounds. The in vitro study indicated that compound 4b could be a promising anti-cancer drug, to be further developed in animal models of cancer. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.010
• 作为产物：
  描述：

  1-甲基吡唑-4-羧酸 在 氯化亚砜 作用下， 以 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 4.0h， 生成 1-methyl-1H-pyrazole-4-carbonyl isothiocyanate
  参考文献：
  名称：

  Synthesis and antimicrobial screening of N-(1-methyl-1H-pyrazole-4-carbonyl)-thiourea derivatives

  摘要：

  In the search of bioactive molecules in the class of functionally 4-substituted pyrazolic compounds, a series of N-(1-methyl-1H-pyrazole-4-carbonyl)-thiourea derivatives were prepared by addition of various substituted anilines to 1-methyl-1H-pyrazole-4-carbonyl isothiocyanate. The new thioureides and the intermediary compounds were characterized by spectroscopic data and elemental analyses and were evaluated for antibacterial and antifungal activities.

  DOI：

  10.1007/s00044-010-9541-9

文献信息

• Aroylguanidine-based factor Xa inhibitors: The discovery of BMS-344577
  作者：Yan Shi、Chi Li、Stephen P. O’Connor、Jing Zhang、Mengxiao Shi、Sharon N. Bisaha、Ying Wang、Doree Sitkoff、Andrew T. Pudzianowski、Christine Huang、Herbert E. Klei、Kevin Kish、Joseph Yanchunas、Eddie C.-K. Liu、Karen S. Hartl、Steve M. Seiler、Thomas E. Steinbacher、William A. Schumacher、Karnail S. Atwal、Philip D. Stein

  DOI：10.1016/j.bmcl.2009.10.084

  日期：2009.12

  We report the design and synthesis of a novel class of N,N′-disubstituted aroylguanidine-based lactam derivatives as potent and orally active FXa inhibitors. The structure–activity relationships (SAR) investigation led to the discovery of the nicotinoyl guanidine 22 as a potent FXa inhibitor (FXa IC50 = 4 nM, EC2×PT = 7 μM). However, the potent CYP3A4 inhibition activity (IC50 = 0.3 μM) of 22 precluded

  我们报告设计和合成的新型的N，N'-二取代的芳基胍基内酰胺衍生物作为有效和口服活性FXa抑制剂。通过结构-活性关系（SAR）研究，发现了烟酰胍22作为有效的FXa抑制剂（FXa IC 50  = 4 nM，EC 2×PT  = 7μM）。然而，有效的CYP3A4抑制活性（IC 50  = 0.3μM）的22排除其进一步发展。对与FXa结合的化合物22的X射线晶体结构的详细分析表明，取代基位于22的烟酰基基团的6位上会暴露在溶剂中，这表明减弱不需要的CYP活性的努力可以集中在这个位置上，而不会显着影响FXa的效力。对6-取代的烟酰胺基胍进行的进一步SAR研究导致发现了6-（二甲基氨基甲酰基）烟酰胍36（BMS-344577，IC 50  = 9 nM，EC 2×PT  = 2.5μM），发现具有选择性，口服有效的FXa抑制剂，在动物模型中具有出色的体外耐受性，良好的药代动力学和药效学。
• Synthesis and antimicrobial screening of N-(1-methyl-1H-pyrazole-4-carbonyl)-thiourea derivatives
  作者：George M. Nitulescu、Constantin Draghici、Mariana C. Chifiriuc、Luminita Marutescu、Coralia Bleotu、Alexandru V. Missir

  DOI：10.1007/s00044-010-9541-9

  日期：2012.3

  In the search of bioactive molecules in the class of functionally 4-substituted pyrazolic compounds, a series of N-(1-methyl-1H-pyrazole-4-carbonyl)-thiourea derivatives were prepared by addition of various substituted anilines to 1-methyl-1H-pyrazole-4-carbonyl isothiocyanate. The new thioureides and the intermediary compounds were characterized by spectroscopic data and elemental analyses and were evaluated for antibacterial and antifungal activities.
• Synthesis of new pyrazole derivatives and their anticancer evaluation
  作者：George Mihai Nitulescu、Constantin Draghici、Alexandru Vasile Missir

  DOI：10.1016/j.ejmech.2010.07.064

  日期：2010.11

  A series of functionally substituted pyrazole compounds have been synthesized and evaluated in vitro for their antiproliferative effects on a panel of 60 cellular lines, according to the National Cancer Institute screening protocol. Three of the 12 tested compounds showed moderate antitumor activity, one of them being chosen for the 5-dose assay and presented logGl(50) values up to -5.75. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis and apoptotic activity of new pyrazole derivatives in cancer cell lines
  作者：George Mihai Nitulescu、Constantin Draghici、Octavian Tudorel Olaru、Lilia Matei、Aldea Ioana、Laura Denisa Dragu、Coralia Bleotu

  DOI：10.1016/j.bmc.2015.07.010

  日期：2015.9

  We designed and synthesized new pyrazole thiourea chimeric derivatives and confirmed their structures by NMR and IR spectra. Apoptotic effects were studied in human cancer cells. The N-[(1-methyl-1H-pyrazol-4-yl)carbonyl]-N'-(3-bromophenyl)-thiourea compound (4b) exhibited the highest apoptosis-inducing effect. Compound 4b and the thiazole derivatives, 5b and 6b, increased the expression of tumor necrosis factor receptors TRAIL-R2 and TRAIL-R1, accompanied by down-modulation of pro-caspase 3 levels, and the augmentation of cleaved caspase 3. They also reduced the levels of apoptosis inhibitory proteins and the expression of the heat-shock proteins Hsp27 and Hsp70. All the tested pyrazole derivatives induced a concentration-dependent increase of cells in G2/M phases. The analysis of the experimental data indicates the reduction of Akt phosphorylation as the most probable cellular mechanism of action for the tested compounds. The in vitro study indicated that compound 4b could be a promising anti-cancer drug, to be further developed in animal models of cancer. (C) 2015 Elsevier Ltd. All rights reserved.