(S)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate | 1613045-94-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate
• 英文别名: [(3S)-1-methyl-3-piperidyl] 2-hydroxy-2,2-diphenyl-acetate；[(3S)-1-methylpiperidin-3-yl] 2-hydroxy-2,2-diphenylacetate
• CAS: 1613045-94-5
• 化学式: C₂₀H₂₃NO₃
• 分子量: 325.408
• InChiKey: ZBEILXWHVSVDBN-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  溴甲烷 、 (S)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.0h， 以934 mg的产率得到(S)-mepenzolate bromide
  参考文献：
  名称：

  Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities

  摘要：

  Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and airflow limitations. We recently proposed that the muscarinic antagonist mepenzolate bromide (mepenzolate) would be therapeutically effective against COPD due to its muscarinic receptor-dependent bronchodilatory activity as well as anti-inflammatory properties. Mepenzolate has an asymmetric carbon atom, thus providing us with the opportunity to synthesize both of its enantiomers ((R)- and (S)-mepenzolate) and to examine their biochemical and pharmacological activities. (R)- or (S)-mepenzolate was synthesized by condensation of benzilic acid with (R)- or (S)-alcohol, respectively, followed by quaternization of the tertiary amine. As predicted by computational simulation, a filter-binding assay in vitro revealed that (R)-mepenzolate showed a higher affinity for the muscarinic M3 receptor than (S)-mepenzolate. In vivo, the bronchodilatory activity of (R)-mepenzolate was superior to that of (S)-mepenzolate, whereas anti-inflammatory activity was indistinguishable between the two enantiomers. We confirmed that each mepenzolate maintained its original stereochemistry in the lung when administered intratracheally. These results suggest that (R)-mepenzolate may have superior properties to (S)-mepenzolate as a drug to treat COPD patients given that the former has more potent bronchodilatory activity than the latter. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.029
• 作为产物：
  描述：

  (S)-1-甲基-3-羟基哌啶 、 二苯基羟基乙酸 在 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.25h， 生成 (S)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate
  参考文献：
  名称：

  Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities

  摘要：

  Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and airflow limitations. We recently proposed that the muscarinic antagonist mepenzolate bromide (mepenzolate) would be therapeutically effective against COPD due to its muscarinic receptor-dependent bronchodilatory activity as well as anti-inflammatory properties. Mepenzolate has an asymmetric carbon atom, thus providing us with the opportunity to synthesize both of its enantiomers ((R)- and (S)-mepenzolate) and to examine their biochemical and pharmacological activities. (R)- or (S)-mepenzolate was synthesized by condensation of benzilic acid with (R)- or (S)-alcohol, respectively, followed by quaternization of the tertiary amine. As predicted by computational simulation, a filter-binding assay in vitro revealed that (R)-mepenzolate showed a higher affinity for the muscarinic M3 receptor than (S)-mepenzolate. In vivo, the bronchodilatory activity of (R)-mepenzolate was superior to that of (S)-mepenzolate, whereas anti-inflammatory activity was indistinguishable between the two enantiomers. We confirmed that each mepenzolate maintained its original stereochemistry in the lung when administered intratracheally. These results suggest that (R)-mepenzolate may have superior properties to (S)-mepenzolate as a drug to treat COPD patients given that the former has more potent bronchodilatory activity than the latter. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.029

文献信息

• Compounds as anti-tubercular agents
  申请人：SPHAERA PHARMA PVT. LTD.

  公开号：US10100012B2

  公开（公告）日：2018-10-16

  The present invention relates to novel compounds of formula (1): The present invention also discloses compounds of formula (1) along with other pharmaceutical acceptable excipients and use of the compounds as anti-tubercular agents.

  本发明涉及式（1）的新型化合物：本发明还公开了式(1)化合物与其他药物可接受的赋形剂以及这些化合物作为抗结核剂的用途。
• NOVEL COMPOUNDS AS ANTI-TUBERCULAR AGENTS
  申请人：Sphaera Pharma Pvt. Ltd.

  公开号：EP3148518A2

  公开（公告）日：2017-04-05
• [EN] NOVEL COMPOUNDS AS ANTI-TUBERCULAR AGENTS<br/>[FR] NOUVEAUX COMPOSÉS UTILISÉS COMME AGENTS ANTI-TUBERCULEUX
  申请人：SPHAERA PHARMA PRIVATE LTD

  公开号：WO2015181837A2

  公开（公告）日：2015-12-03

  The present invention relates to novel compounds of formula (1): The present invention also discloses compounds of formula (1) along with other pharmaceutical acceptable excipients and use of the compounds as anti-tubercular agents.
• Synthesis and biological comparison of enantiomers of mepenzolate bromide, a muscarinic receptor antagonist with bronchodilatory and anti-inflammatory activities
  作者：Yasunobu Yamashita、Ken-Ichiro Tanaka、Teita Asano、Naoki Yamakawa、Daisuke kobayashi、Tomoaki Ishihara、Kengo Hanaya、Mitsuru Shoji、Takeshi Sugai、Mitsuhito Wada、Tadaaki Mashimo、Yoshifumi Fukunishi、Tohru Mizushima

  DOI：10.1016/j.bmc.2014.04.029

  日期：2014.7

  Chronic obstructive pulmonary disease (COPD) is characterized by abnormal inflammatory responses and airflow limitations. We recently proposed that the muscarinic antagonist mepenzolate bromide (mepenzolate) would be therapeutically effective against COPD due to its muscarinic receptor-dependent bronchodilatory activity as well as anti-inflammatory properties. Mepenzolate has an asymmetric carbon atom, thus providing us with the opportunity to synthesize both of its enantiomers ((R)- and (S)-mepenzolate) and to examine their biochemical and pharmacological activities. (R)- or (S)-mepenzolate was synthesized by condensation of benzilic acid with (R)- or (S)-alcohol, respectively, followed by quaternization of the tertiary amine. As predicted by computational simulation, a filter-binding assay in vitro revealed that (R)-mepenzolate showed a higher affinity for the muscarinic M3 receptor than (S)-mepenzolate. In vivo, the bronchodilatory activity of (R)-mepenzolate was superior to that of (S)-mepenzolate, whereas anti-inflammatory activity was indistinguishable between the two enantiomers. We confirmed that each mepenzolate maintained its original stereochemistry in the lung when administered intratracheally. These results suggest that (R)-mepenzolate may have superior properties to (S)-mepenzolate as a drug to treat COPD patients given that the former has more potent bronchodilatory activity than the latter. (C) 2014 Elsevier Ltd. All rights reserved.