(S)-mepenzolate bromide | 92842-82-5

• 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)-mepenzolate bromide
• 英文别名: [(3S)-1,1-dimethylpiperidin-1-ium-3-yl] 2-hydroxy-2,2-diphenylacetate;bromide
• CAS: 92842-82-5
• 化学式: Br*C₂₁H₂₆NO₃
• 分子量: 420.346
• InChiKey: JRRNZNSGDSFFIR-FYZYNONXSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.29
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  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

文献信息

• Optically Active Form of Mepenzolate, and Ameliorating Agent for Chronic Obstructive Pulmonary Disease Which Contains Same as Active Ingredient
  申请人：LTT BIO-PHARMA CO., LTD.

  公开号：US20160368873A1

  公开（公告）日：2016-12-22

  An optically active form of mepenzolate bromide is provided. An agent for ameliorating chronic obstructive pulmonary disease that contains the optically active form as an active ingredient and is based on a bronchodilator effect and an anti-inflammatory effect is also provided. (3R)- or (3S)-3-[(hydroxy)(diphenyl)acetoxy]-1,1-dimethylpiperidinium bromide (hereinafter referred to as “(R)- or (S)-mepenzolate bromide”) is provided. An agent for ameliorating chronic obstructive pulmonary disease that contains the (R)- or (S)-mepenzolate bromide as an active ingredient is provided. Furthermore, an agent for ameliorating chronic obstructive pulmonary disease whose mode of administration is airway administration or inhalation administration is provided.

  提供了一种旋光性的溴化美普托仑。还提供了一种以支气管扩张剂作用和抗炎作用为基础，含有该旋光性形式作为活性成分的改善慢性阻塞性肺病的药剂。提供了(3R)-或(3S)-3-[(羟基)(二苯基)乙氧基]-1,1-二甲基哌啶溴化物（以下简称为“(R)-或(S)-美普托隆溴化物”）。提供了一种含有(R)-或(S)-美普托隆溴化物作为活性成分的改善慢性阻塞性肺病的药剂。此外，还提供了一种以气道给药或吸入给药为给药方式的改善慢性阻塞性肺病的药剂。
• OPTICALLY ACTIVE FORM OF MEPENZOLATE, AND AMELIORATING AGENT FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHICH CONTAINS SAME AS ACTIVE INGREDIENT
  申请人：LTT Bio-Pharma Co., Ltd.

  公开号：EP3109232A1

  公开（公告）日：2016-12-28

  An optically active form of mepenzolate bromide is provided. An agent for ameliorating chronic obstructive pulmonary disease that contains the optically active form as an active ingredient and is based on a bronchodilator effect and an anti-inflammatory effect is also provided. (3R)- or (3S)-3-[(hydroxy)(diphenyl)acetoxy]-1,1-dimethylpiperidinium bromide (hereinafter referred to as "(R)- or (S)-mepenzolate bromide") is provided. An agent for ameliorating chronic obstructive pulmonary disease that contains the (R)- or (S)-mepenzolate bromide as an active ingredient is provided. Furthermore, an agent for ameliorating chronic obstructive pulmonary disease whose mode of administration is airway administration or inhalation administration is provided.

  本研究提供了一种具有光学活性的溴化甲苄醇。此外，还提供了一种用于改善慢性阻塞性肺病的制剂，该制剂以光学活性形式作为活性成分，具有支气管扩张作用和抗炎作用。(提供了(3R)-或(3S)-3-[(羟基)(二苯基)乙酰氧基]-1,1-二甲基哌啶溴化物（以下简称为"(R)-或(S)-甲哌唑溴化物"）。提供了一种用于改善慢性阻塞性肺病的制剂，该制剂含有(R)-或(S)-mepenzolate 溴化物作为活性成分。此外，还提供了一种用于改善慢性阻塞性肺病的制剂，其给药方式为气道给药或吸入给药。
• [EN] OPTICALLY ACTIVE FORM OF MEPENZOLATE, AND AMELIORATING AGENT FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE WHICH CONTAINS SAME AS ACTIVE INGREDIENT<br/>[FR] FORME OPTIQUEMENT ACTIVE DU MÉPENZOLATE, ET AGENT DE SOULAGEMENT POUR BRONCHOPNEUMOPATHIE CHRONIQUE OBSTRUCTIVE QUI CONTIENT CELLE-CI EN TANT QUE PRINCIPE ACTIF<br/>[JA] メペンゾラート光学活性体及びそれを有効成分とする慢性閉塞性肺疾患改善剤
  申请人：LTT BIO PHARMA CO LTD

  公开号：WO2015122031A1

  公开（公告）日：2015-08-20

  　メペンゾラート臭化物の光学活性体を提供し、またかかる光学活性体を有効成分として含有する気管支拡張作用及び抗炎症作用に基づく慢性閉塞性肺疾患改善剤を提供することであり、（３Ｒ）又は（３Ｓ）－３－［（ヒドロキシ）（ジフェニル）アセトキシ］－１，１－ジメチルピペリジニウム　ブロマイド（以下、「（Ｒ）又は（Ｓ）－メペンゾラート臭化物」という）であり、係る（Ｒ）又は（Ｓ）－メペンゾラート臭化物を有効成分として含有する慢性閉塞性肺疾患改善剤であり、また、投与形態が、経気道投与又は吸入投与である慢性閉塞性肺疾患改善剤である。