N-[4-bromo-3-(trifluoromethyl)phenyl]-2-(4-oxo-3H-phthalazin-1-yl)acetamide | 1245749-90-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-[4-bromo-3-(trifluoromethyl)phenyl]-2-(4-oxo-3H-phthalazin-1-yl)acetamide
• CAS: 1245749-90-9
• 化学式: C₁₇H₁₁BrF₃N₃O₂
• 分子量: 426.192
• InChiKey: FSRJJERAIVKGBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ethyl [(E)-3-oxo-1,3-dihydroisobenzofuran-1-ylidene]acetate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 5.0h， 生成 N-[4-bromo-3-(trifluoromethyl)phenyl]-2-(4-oxo-3H-phthalazin-1-yl)acetamide
  参考文献：
  名称：

  Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum

  摘要：

  Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C parvum infection is also presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.037

文献信息

• Compounds and Methods for Treating Mammalian Gastrointestinal Microbial Infections
  申请人：Brandeis University

  公开号：US20150099781A1

  公开（公告）日：2015-04-09

  Described herein are compounds, and pharmaceutically acceptable salts and prodrugs thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound of the invention selectively inhibits a parasitic IMPDH versus a host IMPDH. Further, the invention provides pharmaceutical compositions comprising one or more compounds of the invention. The invention also relates to methods of treating various parasitic and bacterial infections in mammals. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.

  本文描述了一些化合物及其药学上可接受的盐和前药，它们可用作IMPDH的抑制剂。在某些实施例中，本发明的一种化合物能够选择性地抑制寄生物的IMPDH而不影响宿主的IMPDH。此外，本发明提供了包括一种或多种本发明化合物的药物组合物。本发明还涉及用于治疗哺乳动物中各种寄生虫和细菌感染的方法。此外，这些化合物可以单独使用或与其他治疗或预防药物如抗病毒药、抗炎药、抗微生物药和免疫抑制剂等联合使用。
• US8969342B2
  申请人：——

  公开号：US8969342B2

  公开（公告）日：2015-03-03
• [EN] COMPOUNDS AND METHODS FOR TREATING MAMMALIAN GASTROINTESTINAL MICROBIAL INFECTIONS<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR TRAITER LES INFECTIONS MICROBIENNES GASTRO-INTESTINALES MAMMALIENNES
  申请人：UNIV BRANDEIS

  公开号：WO2010108187A2

  公开（公告）日：2010-09-23

  Described herein are compounds, and pharmaceutically acceptable salts and prodrugs thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound of the invention selectively inhibits a parasitic IMPDH versus a host IMPDH. Further, the invention provides pharmaceutical compositions comprising one or more compounds of the invention. The invention also relates to methods of treating various parasitic and bacterial infections in mammals. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.
• Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum
  作者：Corey R. Johnson、Suresh Kumar Gorla、Mandapati Kavitha、Minjia Zhang、Xiaoping Liu、Boris Striepen、Jan R. Mead、Gregory D. Cuny、Lizbeth Hedstrom

  DOI：10.1016/j.bmcl.2012.12.037

  日期：2013.2

  Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C parvum infection is also presented. (C) 2012 Elsevier Ltd. All rights reserved.