N-(4-chloro-3-methyl-phenyl)-2-(3-methyl-4-oxo-phthalazin-1-yl)acetamide | 1422284-88-5

• 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-chloro-3-methyl-phenyl)-2-(3-methyl-4-oxo-phthalazin-1-yl)acetamide
• 英文别名: N-(4-chloro-3-methylphenyl)-2-(3-methyl-4-oxophthalazin-1-yl)acetamide
• CAS: 1422284-88-5
• 化学式: C₁₈H₁₆ClN₃O₂
• 分子量: 341.797
• InChiKey: JPTUPRPBQCUKMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  3

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 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-chloro-3-methyl-phenyl)-2-(3-methyl-4-oxo-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

• [EN] COMPOUNDS AND METHODS FOR TREATING MAMMALIAN GASTROINTESTINAL MICROBIAL INFECTIONS<br/>[FR] COMPOSÉS ET PROCÉDÉS DE TRAITEMENT D'INFECTIONS MICROBIENNES GASTRO-INTESTINALES DE MAMMIFÈRE
  申请人：UNIV BRANDEIS

  公开号：WO2014028931A2

  公开（公告）日：2014-02-20

  Disclosed are compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound selectively inhibits a parasitic IMPDH versus a host IMPDH. Also disclosed are pharmaceutical compositions comprising one or more compounds of the invention. Related methods of treating various parasitic and bacterial infections in mammals are disclosed. 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.