tert-butyl 2-((chlorocarbonyl)(methyl)amino)acetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: tert-butyl 2-((chlorocarbonyl)(methyl)amino)acetate
• 英文别名: tert-butyl 2-[carbonochloridoyl(methyl)amino]acetate
• 化学式: C₈H₁₄ClNO₃
• 分子量: 207.657
• InChiKey: BZEWHLHTBGXZMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-((chlorocarbonyl)(methyl)amino)acetate 、 N-[3,5-双(三氟甲基)苯基]-5-氯-2-羟基苯甲酰胺 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 14.0h， 以75.1%的产率得到Tert-butyl 2-[[2-[[3,5-bis(trifluoromethyl)phenyl]carbamoyl]-4-chlorophenoxy]carbonyl-methylamino]acetate
  参考文献：
  名称：

  Salicylanilide Inhibitors of Toxoplasma gondii

  摘要：

  Toxoplasma gondii (T. gondii) is an apicomplexan parasite that can cause eye disease, brain disease, and death, especially in congenitally infected and immune-compromised people. Novel medicines effective against both active and latent forms of the parasite are greatly needed. The current study focused on the discovery of such medicines by exploring a family of potential inhibitors whose antiapicomplexan activity has not been previously reported. Initial screening efforts revealed that niclosamide, a drug approved for anthelmintic use, possessed promising activity in vitro against T. gondii. This observation inspired the evaluation of the activity of a series of salicylanilides and derivatives. Several inhibitors with activities in the nanomolar range with no appreciable in vitro toxicity to human cells were identified. An initial structure activity relationship was explored. Four compounds were selected for evaluation in an in vivo model of infection, and two derivatives with potentially enhanced pharmacological parameters demonstrated the best activity profiles.

  DOI：

  10.1021/jm3007596
• 作为产物：
  描述：

  sarcosine t-butyl ester hydrochloride 在 碳酸氢钠 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 tert-butyl 2-((chlorocarbonyl)(methyl)amino)acetate
  参考文献：
  名称：

  Method of use of pharmaceutical formulations for the treatment of apicomplexan diseases in animals

  摘要：

  本发明涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物单独或与一个或多个其他活性或赋形剂药物物质结合而成。本发明进一步涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物的组合构成。本发明进一步涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物的组合构成，进一步包括一个或多个活性或赋形剂药物物质。

  公开号：

  US20130324555A1

文献信息

• Synthesis and Evaluation of Carbamate Prodrugs of a Phenolic Compound
  作者：Yasushi Igarashi、Erika Yanagisawa、Toshihiro Ohshima、Shuichi Takeda、Masaki Aburada、Ken-ichi Miyamoto

  DOI：10.1248/cpb.55.328

  日期：——

  A series of carbamates of the phenolic compound 1 were prepared and evaluated in vivo as its prodrug. Each carbamate was orally administered to rats, and plasma concentrations of the parent compound 1 were measured with the passage of time. We judged which carbamate was suitable for the prodrug of 1 from both the AUC value of 1 and absence of the carbamate in plasma. The AUC value of 1 after oral administration of 2b was approximately 40-fold higher than that for an administration of 1, and the bioconversion from 2b to 1 was excellent. As a whole, di-substituted carbamates resulted in higher plasma concentrations of 1 than did mono-substituted ones. However di-substituted carbamates were almost always detected in plasma. As a result, we found that the ethycarbamoyl derivative 2b demonstrates the best prodrug property in this series.

  酚类化合物1的一系列氨基甲酸酯被制备并作为前药在体内进行了评估。每种氨基甲酸酯被口服给予大鼠，并随着时间的推移测量母体化合物1的血浆浓度。我们从1的AUC值和血浆中无氨基甲酸酯存在这两方面来判断哪种氨基甲酸酯适合作为1的前药。口服给予2b后1的AUC值大约是直接给予1的40倍，且2b向1的生物转化非常出色。总体而言，双取代氨基甲酸酯导致1的血浆浓度高于单取代氨基甲酸酯。然而双取代氨基甲酸酯几乎总是被检测到在血浆中存在。因此，我们发现乙氨基甲酸酯衍生物2b在这一系列中显示出最佳的前药特性。
• Method of use of pharmaceutical formulations for the treatment of apicomplexan diseases in animals
  申请人：Wood Richard Delarey

  公开号：US20130324555A1

  公开（公告）日：2013-12-05

  The present invention is directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a salicylanilide or salicylanilide derivative, disclosed herein, alone or in combination with one or more other active or excipient pharmaceutical substances. The present invention is further directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a combination of salicylanilides or salicylanilide derivatives, disclosed herein. The present invention is further directed to the method of use of effective pharmaceutical formulations for the treatment of diseases caused by apicomplexan parasites, said formulation comprised of a combination of salicylanilides or salicylanilide derivatives, disclosed herein, further comprised of one or more active or excipient pharmaceutical substances.

  本发明涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物单独或与一个或多个其他活性或赋形剂药物物质结合而成。本发明进一步涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物的组合构成。本发明进一步涉及有效药物配方的使用方法，用于治疗由顶复合体寄生虫引起的疾病，所述配方由本文披露的水杨酰苯胺或水杨酰苯胺衍生物的组合构成，进一步包括一个或多个活性或赋形剂药物物质。
• Salicylanilide Inhibitors of Toxoplasma gondii
  作者：Alina Fomovska、Richard D. Wood、Ernest Mui、Jitenter P. Dubey、Leandra R. Ferreira、Mark R. Hickman、Patricia J. Lee、Susan E. Leed、Jennifer M. Auschwitz、William J. Welsh、Caroline Sommerville、Stuart Woods、Craig Roberts、Rima McLeod

  DOI：10.1021/jm3007596

  日期：2012.10.11

  Toxoplasma gondii (T. gondii) is an apicomplexan parasite that can cause eye disease, brain disease, and death, especially in congenitally infected and immune-compromised people. Novel medicines effective against both active and latent forms of the parasite are greatly needed. The current study focused on the discovery of such medicines by exploring a family of potential inhibitors whose antiapicomplexan activity has not been previously reported. Initial screening efforts revealed that niclosamide, a drug approved for anthelmintic use, possessed promising activity in vitro against T. gondii. This observation inspired the evaluation of the activity of a series of salicylanilides and derivatives. Several inhibitors with activities in the nanomolar range with no appreciable in vitro toxicity to human cells were identified. An initial structure activity relationship was explored. Four compounds were selected for evaluation in an in vivo model of infection, and two derivatives with potentially enhanced pharmacological parameters demonstrated the best activity profiles.