1-oxo-3-(pyridin-3-yl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid | 1620486-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-oxo-3-(pyridin-3-yl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid
• 英文别名: rac-(3R,4R)-1-oxo-3-(pyridin-3-yl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid, trans；(3S,4S)-1-oxo-3-pyridin-3-yl-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinoline-4-carboxylic acid
• CAS: 1620486-50-1
• 化学式: C₁₇H₁₃F₃N₂O₃
• 分子量: 350.297
• InChiKey: PBUPDIAWZXEDNZ-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  70.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (E)-2,2,2-trifluoro-N-(pyridin-3-ylmethylene)ethanamine 在 溶剂黄146 作用下， 以 正庚烷 、 氯仿 、 水 为溶剂， 反应 69.67h， 生成 1-oxo-3-(pyridin-3-yl)-2-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid
  参考文献：
  名称：

  N-甲基咪唑促进同邻苯二甲酸酐与亚胺反应

  摘要：

  将N-甲基咪唑 (NMI) 添加到同邻苯二甲酸酐与亚胺如吡啶-3-甲醛-N-三氟乙基亚胺( 9 ) 的反应中减少了消除副产物的量并提高了缩甲醛环加合物四氢异喹诺酮羧酸酯10的产率。这些化合物的羧酰苯胺作为潜在的抗疟剂是令人感兴趣的。提出了一种合理化 NMI 作用的机制，并描述了10的合成和分辨率的克级程序。

  DOI：

  10.1021/jo501316m

文献信息

• Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides
  作者：David M. Floyd、Philip Stein、Zheng Wang、Jian Liu、Steve Castro、Julie A. Clark、Michele Connelly、Fangyi Zhu、Gloria Holbrook、Amy Matheny、Martina S. Sigal、Jaeki Min、Rajkumar Dhinakaran、Senthil Krishnan、Sridevi Bashyum、Spencer Knapp、R. Kiplin Guy

  DOI：10.1021/acs.jmedchem.6b00752

  日期：2016.9.8

  Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(35,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate.