| 1322094-73-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• CAS: 1322094-73-4
• 化学式: C₂₃H₁₆N₂O₃
• 分子量: 368.392
• InChiKey: TVJYPLMMXFMZJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.85
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  79.29
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  、 2-amino-N-[(4-fluorophenyl)methyl]-N-methyl-2-phenylacetamide hydrochloride 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-[2-[(4-fluorophenyl)methyl-methylamino]-2-oxo-1-phenylethyl]-2-[(2-phenylbenzoyl)amino]quinoline-6-carboxamide
  参考文献：
  名称：

  Discovery of microsomal triglyceride transfer protein (MTP) inhibitors with potential for decreased active metabolite load compared to dirlotapide

  摘要：

  Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activity of likely human metabolites and increasing metabolite clearance to reduce exposure. Introduction of 4'-alkyl and 4'-alkoxy substituents afforded compounds exhibiting improved therapeutic index in rats with respect to liver triglyceride accumulation and enzyme elevation. Likely human metabolites of select compounds were prepared and characterized for their potential to inhibit MTP in vivo. Based on preclinical efficacy and safety data and its potential for producing short-lived, weakly active metabolites, compound 13 (PF-02575799) advanced into phase 1 clinical studies. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.099
• 作为产物：
  描述：

  喹啉-6-羧酸 在 4-二甲氨基吡啶 、 苯酐 、 lithium hydroxide monohydrate 、 过氧化脲素 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  Discovery of microsomal triglyceride transfer protein (MTP) inhibitors with potential for decreased active metabolite load compared to dirlotapide

  摘要：

  Analogues related to dirlotapide (1), a gut-selective inhibitor of microsomal triglyceride transfer protein (MTP) were prepared with the goal of further reducing the potential for unwanted liver MTP inhibition and associated side-effects. Compounds were designed to decrease active metabolite load: reducing MTP activity of likely human metabolites and increasing metabolite clearance to reduce exposure. Introduction of 4'-alkyl and 4'-alkoxy substituents afforded compounds exhibiting improved therapeutic index in rats with respect to liver triglyceride accumulation and enzyme elevation. Likely human metabolites of select compounds were prepared and characterized for their potential to inhibit MTP in vivo. Based on preclinical efficacy and safety data and its potential for producing short-lived, weakly active metabolites, compound 13 (PF-02575799) advanced into phase 1 clinical studies. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.099