2-(2-三氟甲基-己基)-异吲哚-1,3-二酮 | 1026470-35-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: 2-(2-三氟甲基-己基)-异吲哚-1,3-二酮
• 英文名称: 2-(2-Trifluoromethyl-hexyl)-isoindole-1,3-dione
• 英文别名: 2-[2-(Trifluoromethyl)hexyl]isoindole-1,3-dione
• CAS: 1026470-35-8
• 化学式: C₁₅H₁₆F₃NO₂
• 分子量: 299.293
• InChiKey: KRWAKLMJQLIGQR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-三氟甲基-己基)-异吲哚-1,3-二酮 在 4-二甲氨基吡啶 、 一水合肼 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 3-Methoxy-4-[1-methyl-5-(2-trifluoromethyl-hexylcarbamoyl)-1H-indol-3-ylmethyl]-benzoic acid methyl ester
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4

  摘要：

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.

  DOI：

  10.1021/jm00035a008
• 作为产物：
  描述：

  正丁基丙二酸二乙酯 在 potassium fluoride 、 lithium aluminium tetrahydride 、 sodium hydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 、 二甲基亚砜 为溶剂， 反应 18.5h， 生成 2-(2-三氟甲基-己基)-异吲哚-1,3-二酮
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4

  摘要：

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.

  DOI：

  10.1021/jm00035a008