3-(2-{3-[2-(7-chloro-2-quinolinyl)-(E)-ethenyl]phenyl}-(S)-2-hydroxyethyl)-(S)-3H-isobenzofuran-1-one | 184764-52-1

• 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
• 英文名称: 3-(2-{3-[2-(7-chloro-2-quinolinyl)-(E)-ethenyl]phenyl}-(S)-2-hydroxyethyl)-(S)-3H-isobenzofuran-1-one
• 英文别名: (3R)-3-[(2S)-2-[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-2-hydroxyethyl]-3H-2-benzofuran-1-one
• CAS: 184764-52-1
• 化学式: C₂₇H₂₀ClNO₃
• 分子量: 441.914
• InChiKey: BDRQGMUOCFFGGD-VUBCVZIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-{3-[2-(7-chloro-2-quinolinyl)-(E)-ethenyl]phenyl}-(S)-2-hydroxyethyl)-(S)-3H-isobenzofuran-1-one 在 正丁基锂 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.25h， 生成 2-[1-[[(1R)-1-[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-2-[(1R)-3-oxo-1H-2-benzofuran-1-yl]ethyl]sulfanylmethyl]cyclopropyl]acetic acid
  参考文献：
  名称：

  Synthesis of Montelukast (MK-0476) Metabolic Oxidation Products

  摘要：

  We report the chemical synthesis of six oxidized derivatives of MK-0476 (Montelukast, L-706631), which have been key tools in the identification of its metabolites. We have prepared three diastereoisomeric pairs of potential oxidative metabolites of MK-0476, starting from the (S)-hydroxy ester 7 in 10 and five steps, and starting from MK-0476 itself in one step. The key benzylic hydroxyl of 1 and 2 was introduced by a bromination and saponification reaction sequence. In the case of the hydroxyl of 3 and 4, the key step was the addition of a hydroxymethyl carbanion equivalent on ketone 20. The two sulfoxide 5 and 6 were prepared by a direct oxidation of MK-0476 with m-chloroperbenzoic acid.

  DOI：

  10.1021/jo9615817
• 作为产物：
  描述：

  [S-(E)]-2-[3-[3-[2-(7-氯-2-喹啉基)乙烯基]苯基]-3-羟基丙基]苯甲酸甲酯 在 4-二甲氨基吡啶 、 lithium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 三氟乙酸 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 为溶剂， 反应 29.25h， 生成 3-(2-{3-[2-(7-chloro-2-quinolinyl)-(E)-ethenyl]phenyl}-(S)-2-hydroxyethyl)-(S)-3H-isobenzofuran-1-one
  参考文献：
  名称：

  Synthesis of Montelukast (MK-0476) Metabolic Oxidation Products

  摘要：

  We report the chemical synthesis of six oxidized derivatives of MK-0476 (Montelukast, L-706631), which have been key tools in the identification of its metabolites. We have prepared three diastereoisomeric pairs of potential oxidative metabolites of MK-0476, starting from the (S)-hydroxy ester 7 in 10 and five steps, and starting from MK-0476 itself in one step. The key benzylic hydroxyl of 1 and 2 was introduced by a bromination and saponification reaction sequence. In the case of the hydroxyl of 3 and 4, the key step was the addition of a hydroxymethyl carbanion equivalent on ketone 20. The two sulfoxide 5 and 6 were prepared by a direct oxidation of MK-0476 with m-chloroperbenzoic acid.

  DOI：

  10.1021/jo9615817

文献信息

• HETEROARYL DIOL ACIDS AS LEUKOTRIENE ANTAGONISTS
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0840728A1

  公开（公告）日：1998-05-13
• US5750539A
  申请人：——

  公开号：US5750539A

  公开（公告）日：1998-05-12
• [EN] HETEROARYL DIOL ACIDS AS LEUKOTRIENE ANTAGONISTS<br/>[FR] ACIDES D'HETEROARYLE DIOL ANTAGONISTES DES LEUCOTRIENES
  申请人：MERCK FROSST CANADA INC.

  公开号：WO1996040638A1

  公开（公告）日：1996-12-19

  (EN) Compounds of formula (I) are antagonists of the actions of leukotrienes. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.(FR) L'invention se rapporte à des composés antagonistes des leucotriènes, qui sont représentés par la formule (I). Ces composés sont utiles comme agents anti-asmathiques, anti-allergiques, anti-inflammatoires et cytoprotecteurs. Ils sont également utiles dans le traitement de l'angine de poitrine, des spasmes cérébraux, de la glomérulonéphrite, de l'hépatite, de l'endotoxémie, de l'uvéité et du rejet d'allogreffes.
• Synthesis of Montelukast (MK-0476) Metabolic Oxidation Products
  作者：Claude Dufresne、Michel Gallant、Yves Gareau、Réjean Ruel、Laird Trimble、Marc Labelle

  DOI：10.1021/jo9615817

  日期：1996.1.1

  We report the chemical synthesis of six oxidized derivatives of MK-0476 (Montelukast, L-706631), which have been key tools in the identification of its metabolites. We have prepared three diastereoisomeric pairs of potential oxidative metabolites of MK-0476, starting from the (S)-hydroxy ester 7 in 10 and five steps, and starting from MK-0476 itself in one step. The key benzylic hydroxyl of 1 and 2 was introduced by a bromination and saponification reaction sequence. In the case of the hydroxyl of 3 and 4, the key step was the addition of a hydroxymethyl carbanion equivalent on ketone 20. The two sulfoxide 5 and 6 were prepared by a direct oxidation of MK-0476 with m-chloroperbenzoic acid.