fexinidazole sulfone | 64570-18-9

• 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: fexinidazole sulfone
• 英文别名: 1-methyl-2-[(4-methylsulfonylphenoxy)methyl]-5-nitroimidazole
• CAS: 64570-18-9
• 化学式: C₁₂H₁₃N₃O₅S
• 分子量: 311.318
• InChiKey: YMIAMMYJWRZXIX-UHFFFAOYSA-N

物化性质

• 沸点：
  603.3±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氟苯甲砜 、 1-甲基-5-硝基-2-羟甲基咪唑 生成 fexinidazole sulfone
  参考文献：
  名称：

  1-Alkyl-2-(phenoxymethyl)-5-nitro-imidazoles and process for their

  摘要：

  1-烷基-2-(苯氧甲基)-5-硝基咪唑类化合物的制备方法被描述，这些化合物对滴虫和阿米巴活性，并且特别适用于治疗阴道滴虫病。

  公开号：

  US04031232A1

文献信息

• Cross-Resistance to Nitro Drugs and Implications for Treatment of Human African Trypanosomiasis
  作者：Antoaneta Y. Sokolova、Susan Wyllie、Stephen Patterson、Sandra L. Oza、Kevin D. Read、Alan H. Fairlamb

  DOI：10.1128/aac.00332-10

  日期：2010.7

  The success of nifurtimox-eflornithine combination therapy (NECT) for the treatment of human African trypanosomiasis (HAT) has renewed interest in the potential of nitro drugs as chemotherapeutics. In order to study the implications of the more widespread use of nitro drugs against these parasites, we examined the in vivo and in vitro resistance potentials of nifurtimox and fexinidazole and its metabolites. Following selection in vitro by exposure to increasing concentrations of nifurtimox, Trypanosoma brucei brucei nifurtimox-resistant clones designated NfxR1 and NfxR2 were generated. Both cell lines were found to be 8-fold less sensitive to nifurtimox than parental cells and demonstrated cross-resistance to a number of other nitro drugs, most notably the clinical trial candidate fexinidazole (∼27-fold more resistant than parental cells). Studies of mice confirmed that the generation of nifurtimox resistance in these parasites did not compromise virulence, and NfxR1 remained resistant to both nifurtimox and fexinidazole in vivo . In the case of fexinidazole, drug metabolism and pharmacokinetic studies indicate that the parent drug is rapidly metabolized to the sulfoxide and sulfone form of this compound. These metabolites retained trypanocidal activity but were less effective in nifurtimox-resistant lines. Significantly, trypanosomes selected for resistance to fexinidazole were 10-fold more resistant to nifurtimox than parental cells. This reciprocal cross-resistance has important implications for the therapeutic use of nifurtimox in a clinical setting and highlights a potential danger in the use of fexinidazole as a monotherapy.

  摘要 硝基呋喃妥因-伊夫洛尼汀联合疗法（NECT）在治疗非洲锥虫病（HAT）方面取得的成功再次激发了人们对硝基药物作为化疗药物的潜力的兴趣。为了研究更广泛地使用硝基药物对这些寄生虫的影响，我们研究了 体内 和 体外 耐药性潜力。经过选择 体外 接触浓度不断增加的硝呋太醇、 布鲁氏锥虫 产生了 NfxR1 和 NfxR2 抗 nifurtimox 克隆。研究发现，这两种细胞系对硝呋太霉素的敏感性比亲代细胞低 8 倍，而且对其他一些硝基药物也表现出交叉抗药性，其中最明显的是临床试验候选药物非西咪唑（抗药性比亲代细胞高 27 倍）。对小鼠的研究证实，这些寄生虫对硝呋太尔制霉素产生抗药性并不影响其毒性，而且 NfxR1 在体内仍对硝呋太尔制霉素和非西尼达唑具有抗药性。 在体内 .关于非昔咪唑，药物代谢和药代动力学研究表明，母药会迅速代谢为亚砜和砜形式的化合物。这些代谢物保留了杀锥虫活性，但对耐硝呋太醇的品系效果较差。值得注意的是，经筛选对非西尼达唑具有抗药性的锥虫对硝呋太霉素的抗药性比亲本细胞高 10 倍。这种相互交叉耐药性对硝呋太尔制霉素在临床上的治疗应用具有重要意义，并凸显了将非西尼达唑用作单一疗法的潜在危险。
• US4031232A
  申请人：——

  公开号：US4031232A

  公开（公告）日：1977-06-21
• 1-Alkyl-2-(phenoxymethyl)-5-nitro-imidazoles and process for their
  申请人：Hoechst Aktiengesellschaft

  公开号：US04031232A1

  公开（公告）日：1977-06-21

  1-Alkyl-2-(phenoxymethyl)-5-nitro-imidazoles are described as well as a process for their manufacture. The compounds are active against trichomonads and amoebae and are especially suitable for the treatment of Fluor genitalis.

  1-烷基-2-(苯氧甲基)-5-硝基咪唑类化合物的制备方法被描述，这些化合物对滴虫和阿米巴活性，并且特别适用于治疗阴道滴虫病。