N-(4-fluorophenyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea | 790-88-5

• 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: N-(4-fluorophenyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea
• 英文别名: N-(4-fluoro-phenyl)-N'-(5-nitro-thiazol-2-yl)-urea；N-(4-Fluor-phenyl)-N'-(5-nitro-thiazol-2-yl)-harnstoff；1-(4-Fluoro-phenyl)-3-(5-nitro-thiazol-2-yl)-urea；1-(4-fluorophenyl)-3-(5-nitro-1,3-thiazol-2-yl)urea
• CAS: 790-88-5
• 化学式: C₁₀H₇FN₄O₃S
• 分子量: 282.255
• InChiKey: VHWLIENBFXTZEV-UHFFFAOYSA-N

物化性质

• 密度：
  1.673±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 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：
  128
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-5-硝基噻唑 、 异氰酸对氟苯基酯 以 甲苯 为溶剂， 反应 12.0h， 以94%的产率得到N-(4-fluorophenyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea
  参考文献：
  名称：

  2-Acylamino-5-nitro-1,3-thiazoles: Preparation and in vitro bioevaluation against four neglected protozoan parasites

  摘要：

  The 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. All compounds were tested in vitro against four neglected protozoan parasites (Giardia intestinalis, Trichomonas vaginalis, Leishmania amazonensis and Trypanosoma cruzi). Acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against G. intestinalis and T. vaginalis, showing nanomolar inhibition. Compound 13 (IC50 = 10 nM), was 536-times more active than metronidazole, and 121-fold more effective than nitazoxanide against G. intestinalis. Compound 14 was 29-times more active than metronidazole and 6.5-fold more potent than nitazoxanide against T. vaginalis. Ureic derivatives 2, 3 and 5 showed moderate activity against L. amazonensis. None of them were active against T. cruzi. Ligand efficiency indexes analysis revealed higher intrinsic quality of the most active 2-acylamino derivatives than nitazoxanide and metronidazole. In silico toxicity profile was also computed for the most active compounds. A very low in vitro mammalian cytotoxicity was obtained for 13 and 14, showing selectivity indexes (SI) of 246,300 and 141,500, respectively. Nitazoxanide showed an excellent leishmanicidal and trypanocidal effect, repurposing this drug as potential new antikinetoplastid parasite compound (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.029

文献信息

• [EN] BROAD SPECTRUM BENZOTHIOPHENE-NITROTHIAZOLIDE AND OTHER ANTIMICROBIALS<br/>[FR] BENZOTHIOPHÈNE-NITROTHIAZOLIDE À SPECTRE LARGE ET AUTRES ANTIMICROBIENS
  申请人：UNIV VIRGINIA

  公开号：WO2010107736A2

  公开（公告）日：2010-09-23

  The invention provides novel antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit antibacterial and antiparasitic action against a wide range of human pathogens. The new classes of compounds show extended action against Gram positive bacteria including MRSA drug resistant pathogens. In the Gram-positive organisms, they specifically target and functionally inhibit microbial attachment to surfaces and biofilm formation. In Gram-negative bacteria, including enteroaggregative E. coli strains, these compounds function as pilicides by inhibiting the assembly of pilin subunits into adhesive filaments. Several of these compounds show potent antimicrobial action against Gram positive bacteria, perhaps involving novel targets. Many of the benzothiophene derivatives exhibit antimicrobial activity in the low micrograms per ml range and in blocking biofilm formation in the nanomolar range; ranges considered are well within the range of utility as therapeutics.
• [EN] COMPOSITIONS AND METHODS FOR TREATING TUBERCULOSIS<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DE LA TUBERCULOSE
  申请人：UNIV VIRGINIA PATENT FOUND

  公开号：WO2012040170A2

  公开（公告）日：2012-03-29

  The invention provides for the use of antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit anti-mycobacteria activity, including the mycobacterium causing tuberculosis. Multiple compounds were synthesized and screened for anti-tuberculosis activity. Disclosed herein are a series of compounds with anti-tuberculosis activity, including six leads that completely inhibited bacterial growth at 5 micrograms per ml or less. Three of these compounds were tested to determine MIC and these ranged between 1 and 4 micrograms per ml against both drug susceptible Mycobacterium tuberculosis strains and strains that are multi-drug resistant (MDR) including XDR strains. The compounds developed are derived from parent compound nitazoxanide, which had no inhibitory activity in the stringent testing format used herein. The derivatives were synthesized using a di-nitro-thiophene or 4-Chloro-5-Nitro-thiazole scaffold and R groups connected via a peptide bond (NHCO) to cyclic compounds such as benzene, thiophene or furans. Many of these compounds have broad spectrum activity against Gram positive bacteria including Staphylococcus aureus (MRSA) and Staphylococcus epidermidis. Several of these lead compounds were not toxic for mice at 200 mg/Kg doses administered over a period of three days.
• 2-Acylamino-5-nitro-1,3-thiazoles: Preparation and in vitro bioevaluation against four neglected protozoan parasites
  作者：Carlos Nava-Zuazo、Fabiola Chávez-Silva、Rosa Moo-Puc、Manuel Jesús Chan-Bacab、Benjamín Otto Ortega-Morales、Hermenegilda Moreno-Díaz、Daniel Díaz-Coutiño、Emanuel Hernández-Núñez、Gabriel Navarrete-Vázquez

  DOI：10.1016/j.bmc.2014.01.029

  日期：2014.3

  The 2-acylamino-5-nitro-1,3-thiazole derivatives (1-14) were prepared using a one step reaction. All compounds were tested in vitro against four neglected protozoan parasites (Giardia intestinalis, Trichomonas vaginalis, Leishmania amazonensis and Trypanosoma cruzi). Acetamide (9), valeroylamide (10), benzamide (12), methylcarbamate (13) and ethyloxamate (14) derivatives were the most active compounds against G. intestinalis and T. vaginalis, showing nanomolar inhibition. Compound 13 (IC50 = 10 nM), was 536-times more active than metronidazole, and 121-fold more effective than nitazoxanide against G. intestinalis. Compound 14 was 29-times more active than metronidazole and 6.5-fold more potent than nitazoxanide against T. vaginalis. Ureic derivatives 2, 3 and 5 showed moderate activity against L. amazonensis. None of them were active against T. cruzi. Ligand efficiency indexes analysis revealed higher intrinsic quality of the most active 2-acylamino derivatives than nitazoxanide and metronidazole. In silico toxicity profile was also computed for the most active compounds. A very low in vitro mammalian cytotoxicity was obtained for 13 and 14, showing selectivity indexes (SI) of 246,300 and 141,500, respectively. Nitazoxanide showed an excellent leishmanicidal and trypanocidal effect, repurposing this drug as potential new antikinetoplastid parasite compound (C) 2014 Elsevier Ltd. All rights reserved.