2-sulfanyl-4,6-difluorobenzoimidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-sulfanyl-4,6-difluorobenzoimidazole
• 英文别名: 2-mercapto-4,6-difluorobenzimidazole；4,6-difluoro-1,3-dihydrobenzimidazole-2-thione
• 化学式: C₇H₄F₂N₂S
• 分子量: 186.185
• InChiKey: YTQXVSYNOOAPJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-sulfanyl-4,6-difluorobenzoimidazole 在 sodium hydroxide 、 碳酸氢钠 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.17h， 生成 4,6-difluoro-2-[(4-methoxypyridin-2-yl)methylsulfinyl]-1H-benzimidazole
  参考文献：
  名称：

  Structure-Activity Relationship of Omeprazole and Analogs as Helicobacter pylori Urease Inhibitors

  摘要：

  Helicobacter pylori urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and a reactive cysteine residue in the active site. The H+/K(+)-ATPase inhibitor omeprazole is a prodrug of a sulfenamide which covalently modifies cysteine residues on the luminal side of the H+/K(+)-ATPase of gastric parietal cells. Omeprazole and eight analogues were selected based on their chemical, electronic, and kinetic properties, and each was incubated with viable H. pylori in phosphate-buffered saline at pH 7.4 for 30 min, after which 100 mM urea was added and the amount of ammonia formed analyzed after a further 10 min. Inhibition between 0% and 100% at a 0.1 mM concentration was observed for the different analogues and could be expressed as a function of the pKa-value of the pyridine, the pKa-value of the benzimidazole, the overall lipophilicity, and, most importantly, the rate of sulfenamide formation, in a quantitative structure-activity relationship. The inhibition was potentiated by a lower pH (favoring the formation of the sulfenamide) but abolished in the presence of beta-mercaptoethanol (a scavenger of the sulfenamide). Structural analogues incapable of yielding the sulfenamide did not inhibit ammonia production. Treatment of Helicobacter felis-infected mice with 230 mumol/kg flurofamide b.i.d. for 4 weeks, known to potently inhibit urease activity in vivo, as a means of eradicating the infection, was tested and compared with the effect of 125 mumol/kg omeprazole b.i.d. for 4 weeks. Neither treatment proved efficacious.

  DOI：

  10.1021/jm00025a008
• 作为产物：
  描述：

  4-氟-2-硝基苯胺 在 sodium tetrahydroborate 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 为溶剂， 反应 16.0h， 生成 2-sulfanyl-4,6-difluorobenzoimidazole
  参考文献：
  名称：

  SAR156497，极光激酶的选择性选择性抑制剂

  摘要：

  丝氨酸/苏氨酸激酶的Aurora家族对于有丝分裂必不可少。已经证明了它们在广泛的恶性肿瘤中的细胞周期调控和异常表达中的关键作用，并促使人们对小分子Aurora抑制剂进行深入研究。实际上，其中超过10种已作为潜在的抗癌疗法进入临床。我们在此报告了一系列新的三环分子的发现和优化，这些分子导致了SAR156497，一种具有体外和体内功效的选择性选择性极光A，B和C抑制剂。我们还提供了有关其与靶蛋白结合模式的见解，这可以解释其选择性。

  DOI：

  10.1021/jm501326k

文献信息

• 1,4-Dihydropyridine-Fused Heterocycles, Process for Preparing the Same, Use and Compositions Containing Them
  申请人：MAUGER Jacques

  公开号：US20080261969A1

  公开（公告）日：2008-10-23

  This invention relates to compounds of formula (I) to processes for the preparation of such compounds, to pharmaceutical compositions comprising such compounds, and to methods of treatment comprising administering of such compounds.

  本发明涉及式(I)化合物、制备该类化合物的方法、包含该类化合物的药物组合物，以及通过给予该类化合物的治疗方法。
• Design, synthesis, and biological evaluation of novel pleuromutilin derivatives containing benzimidazoles as effective anti‐MRSA agents
  作者：Qi‐Wen Zhang、Jie Ren、Jia‐Xun Lu、Xiao‐Ying Chen、Xian‐Jin He、Qi Wang、Zi‐Dan Zhou、Zhen Jin、Zhen‐Ling Zeng、You‐Zhi Tang

  DOI：10.1002/ddr.22095

  日期：2023.11

  A series of pleuromutilin derivatives containing benzimidazole were designed, synthesized, and evaluated for their antibacterial activities against Methicillin-resistant Staphylococcus aureus (MRSA) in this study. The in vitro antibacterial activities of the synthesized derivatives against four strains of S. aureus (MRSA ATCC 43300, S. aureus ATCC 29213, S. aureus 144, and S. aureus AD3) were determined

  本研究设计、合成了一系列含有苯并咪唑的截短侧耳素衍生物，并评价了其对耐甲氧西林金黄色葡萄球菌（MRSA）的抗菌活性。通过肉汤稀释法测定了合成衍生物对四种金黄色葡萄球菌菌株（MRSA ATCC 43300、金黄色葡萄球菌ATCC 29213、金黄色葡萄球菌144 和金黄色葡萄球菌AD3）的体外抗菌活性。在这些衍生物中，化合物58对MRSA（最低抑菌浓度[MIC] = 0.0625 μg/mL）表现出优于泰妙菌素（MIC = 0.5 μg/mL）的体外抗菌作用。与泰妙菌素相比，化合物58对MRSA具有更快的杀菌动力学和更长的抗生素后作用时间。同时，在8 μg/mL浓度下，化合物58对RAW 264.7细胞没有表现出明显的细胞毒作用。此外，在减少小鼠大腿感染模型中的 MRSA 负荷方面，化合物58 (-2.04 log 10 CFU/mL) 表现出比泰妙菌素 (-1.02 log 10 CFU/mL)
• 1,4-DIHYDROPYRIDINE-FUSED HETEROCYCLES, PROCESS FOR PREPARING THE SAME, USE AND COMPOSITIONS CONTAINING THEM
  申请人：Aventis Pharma S.A.

  公开号：EP1910366A2

  公开（公告）日：2008-04-16
• US8163768B2
  申请人：——

  公开号：US8163768B2

  公开（公告）日：2012-04-24
• [EN] 1,4-DIHYDROPYRIDINE-FUSED HETEROCYCLES, PROCESS FOR PREPARING THE SAME, USE AND COMPOSITIONS CONTAINING THEM<br/>[FR] HETEROCYCLES FUSIONNES DE 1,4-DIHYDROPYRIDINE, PROCEDE POUR PREPARER CEUX-CI, UTILISATIONS ET COMPOSITIONS LES CONTENANT
  申请人：AVENTIS PHARMA SA

  公开号：WO2007012972A2

  公开（公告）日：2007-02-01

  [EN] 1,4-Dihydropyridine-fused heterocycles, process for preparing the same, use and compositions containing them. The invention is about substituted dihydropyridine-fused heterocycles useful for the treatment of cancer disease, especially for preventing cancerous cells to divide. These compounds act as inhibitors of Aurora A and/or B kinases. Formula (I).
  [FR] L'invention concerne des hétérocycles fusionnés de 1,4-dihydropyridine, un procédé pour préparer ceux-ci, ainsi que leurs utilisations et des compositions les contenant. L'invention concerne des hétérocycles fusionnés de dihydropyridine utiles pour traiter un cancer, en particulier pour éviter une division de cellules cancéreuses. Ces composés servent d'inhibiteurs aux kinases Aurora A et/ou B. Formule (I).