(4R)-5,5-dimethyl-4-hydroxymethyl-2-phenyl-1,3-dioxane | 1132108-81-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二恶烷
• 英文名称: (4R)-5,5-dimethyl-4-hydroxymethyl-2-phenyl-1,3-dioxane
• 英文别名: [(4R)-5,5-Dimethyl-2-phenyl-1,3-dioxan-4-yl]methan-1-ol；[(4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-yl]methanol
• CAS: 1132108-81-6
• 化学式: C₁₃H₁₈O₃
• 分子量: 222.284
• InChiKey: JKZHXUHXUXISTM-PXYINDEMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R)-5,5-dimethyl-4-hydroxymethyl-2-phenyl-1,3-dioxane 在 sodium azide 、 对硝基苯酚 、 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 4-nitrophenyl-[((4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-yl)methyl]sulfamate
  参考文献：
  名称：

  Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase

  摘要：

  The biosynthesis of pantothenate, the core of coenzyme A (CoA), has been considered an attractive target for the development of antimicrobial agents since this pathway is essential in prokaryotes, but absent in mammals. Pantothenate synthetase, encoded by the gene panC, catalyzes the final condensation of pantoic acid with beta-alanine to afford pantothenate via an intermediate pantoyl adenylate. We describe the synthesis and biochemical characterization of five PanC inhibitors that mimic the intermediate pantoyl adenylate. These inhibitors are competitive inhibitors with respect to pantoic acid and possess submicromolar to micromolar inhibition constants. The observed SAR is rationalized through molecular docking studies based on the reported co-crystal structure of 1a with PanC. Finally, whole cell activity is assessed against wild-type Mtb as well as a PanC knockdown strain where PanC is depleted to less than 5% of wild-type levels. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.017
• 作为产物：
  描述：

  苯甲醛二乙缩醛 、 D-(-)-泛酰内酯 在 camphor-10-sulfonic acid 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以85%的产率得到(4R)-5,5-dimethyl-4-hydroxymethyl-2-phenyl-1,3-dioxane
  参考文献：
  名称：

  Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase

  摘要：

  The biosynthesis of pantothenate, the core of coenzyme A (CoA), has been considered an attractive target for the development of antimicrobial agents since this pathway is essential in prokaryotes, but absent in mammals. Pantothenate synthetase, encoded by the gene panC, catalyzes the final condensation of pantoic acid with beta-alanine to afford pantothenate via an intermediate pantoyl adenylate. We describe the synthesis and biochemical characterization of five PanC inhibitors that mimic the intermediate pantoyl adenylate. These inhibitors are competitive inhibitors with respect to pantoic acid and possess submicromolar to micromolar inhibition constants. The observed SAR is rationalized through molecular docking studies based on the reported co-crystal structure of 1a with PanC. Finally, whole cell activity is assessed against wild-type Mtb as well as a PanC knockdown strain where PanC is depleted to less than 5% of wild-type levels. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.017

文献信息

• [EN] COMPLEX PANTOIC ACID ESTER NEOPENTYL SULFONYL ESTER CYCLIZATION RELEASE PRODRUGS OF ACAMPROSATE, COMPOSITIONS THEREOF, AND METHODS OF USE<br/>[FR] PROMÉDICAMENTS DE LIBÉRATION DE CYCLISATION D'ESTER DE NÉOPENTYLE SULFONYLE D'ESTER D'ACIDE PANTOÏQUE COMPLEXE D'ACAMPROSATE, LEURS COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：XENOPORT INC

  公开号：WO2009033054A1

  公开（公告）日：2009-03-12

  Pantoic acid ester neopentyl sulfonyl ester prodrugs of acamprosate of formula (I), pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorders, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis and pain are disclosed.

  本发明涉及公式（I）的戊二酸酯新戊基磺酰酯前药，包括这种前药的制药组合物，以及使用这种前药和组合物治疗疾病的方法。具体而言，本发明揭示了具有增强口服生物利用度的戊二酸酯前药，并使用这些前药治疗神经退行性疾病、精神疾病、情绪障碍、焦虑症、躯体形式障碍、运动障碍、物质滥用障碍、暴食障碍、皮层扩散性抑制相关障碍、耳鸣、睡眠障碍、多发性硬化和疼痛等疾病的方法。
• COMPLEX PANTOIC ACID ESTER NEOPENTYL SULFONYL ESTER CYCLIZATION RELEASE PRODRUGS OF ACAMPROSATE, COMPOSITIONS THEREOF, AND METHODS OF USE
  申请人：Jandeleit Bernd

  公开号：US20090076147A1

  公开（公告）日：2009-03-19

  Pantoic acid ester neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorder, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis, and pain are disclosed.

  本文公开了帕托酸酯新戊磺酰酯丙戊酸酯前药、包含这种前药的制药组合物以及使用这种前药和组合物治疗疾病的方法。具体而言，本文公开了增强口服生物利用度的丙戊酸酯前药，并公开了使用丙戊酸酯前药治疗神经退行性疾病、精神疾病、情绪障碍、焦虑障碍、躯体形式障碍、运动障碍、物质滥用障碍、暴食症、皮层扩散性抑制相关障碍、耳鸣、睡眠障碍、多发性硬化和疼痛的方法。
• SIMPLE PANTOIC ACID ESTER NEOPENTYL SULFONYL ESTER CYCLIZATION RELEASE PRODRUGS OF ACAMPROSATE, COMPOSITIONS THEREOF, AND METHODS OF USE
  申请人：Jandeleit Bernd

  公开号：US20090082440A1

  公开（公告）日：2009-03-26

  Pantoic acid ester neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorder, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis, and pain are disclosed.

  本发明公开了一种帕昔瑞酸酯类新戊烷磺酰酯前药、包含此类前药的制药组合物以及使用此类前药和组合物治疗疾病的方法。具体而言，本发明公开了表现出增强口服生物利用度的帕昔瑞酸酯前药和使用帕昔瑞酸酯前药治疗神经退行性疾病、精神障碍、情绪障碍、焦虑症、躯体形式障碍、运动障碍、物质滥用障碍、暴食症、皮质扩散性抑制相关障碍、耳鸣、睡眠障碍、多发性硬化症和疼痛的方法。
• Complex pantoic acid ester neopentyl sulfonyl ester cyclization release prodrugs of acamprosate, compositions thereof, and methods of use
  申请人：XenoPort, Inc.

  公开号：US08168617B2

  公开（公告）日：2012-05-01

  Pantoic acid ester neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorder, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis, and pain are disclosed.

  本发明涉及帕昔烷酸酯新戊基磺酰酯前药、包含此类前药的制药组合物以及使用此类前药和组合物治疗疾病的方法。具体来说，本发明揭示了增强口服生物利用度的帕昔烷酸酯前药，以及使用帕昔烷酸酯前药治疗神经退行性疾病、精神障碍、情绪障碍、焦虑障碍、躯体形式障碍、运动障碍、物质滥用障碍、暴食障碍、皮层扩散性抑制相关障碍、耳鸣、睡眠障碍、多发性硬化和疼痛的方法。
• Simple pantoic acid ester neopentyl sulfonyl ester cyclization release prodrugs of acamprosate, compositions thereof, and methods of use
  申请人：XenoPort, Inc.

  公开号：US07994218B2

  公开（公告）日：2011-08-09

  Pantoic acid ester neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs exhibiting enhanced oral bioavailability and methods of using acamprosate prodrugs to treat neurodegenerative disorders, psychotic disorders, mood disorders, anxiety disorders, somatoform disorders, movement disorders, substance abuse disorders, binge eating disorder, cortical spreading depression related disorders, tinnitus, sleeping disorders, multiple sclerosis, and pain are disclosed.

  本发明公开了带有泊酸酯新戊烷磺酰酯前药的阿卡姆普罗酸，包含此类前药的制药组合物以及使用此类前药和其组合物治疗疾病的方法。特别地，本发明公开了表现出口服生物利用度增强的阿卡姆普罗酸前药以及使用阿卡姆普罗酸前药治疗神经退行性疾病、精神障碍、情绪障碍、焦虑障碍、躯体形式障碍、运动障碍、物质滥用障碍、暴食症、皮层扩散性抑制相关障碍、耳鸣、睡眠障碍、多发性硬化和疼痛的方法。