(R)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate | 315680-06-9

• 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: (R)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate
• 英文别名: (R)-t-mepenzolate；hydroxy-diphenyl-acetic acid (R)-1-methyl-piperidin-3-yl ester；[(3R)-1-methylpiperidin-3-yl] 2-hydroxy-2,2-diphenylacetate
• CAS: 315680-06-9
• 化学式: C₂₀H₂₃NO₃
• 分子量: 325.408
• InChiKey: ZBEILXWHVSVDBN-GOSISDBHSA-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 、 (R)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate 以 乙腈 为溶剂， 反应 5.0h， 以77%的产率得到(R)-mepenzolate bromide
  参考文献：
  名称：

  Optically Active Form of Mepenzolate, and Ameliorating Agent for Chronic Obstructive Pulmonary Disease Which Contains Same as Active Ingredient

  摘要：

  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。

  公开号：

  US20160368873A1
• 作为产物：
  描述：

  二苯乙醇酸甲酯 在 10percent Pd/C 高氯酸 、 氢气 、 sodium 、 sodium cyanoborohydride 、 zinc(II) chloride 作用下， 以 甲醇 、 乙醇 、 苯 为溶剂， 反应 26.5h， 生成 (R)-1-methylpiperidin-3-yl 2-hydroxy-2,2-diphenylacetate
  参考文献：
  名称：

  Synthesis, ¹⁸F-Labeling, and Biological Evaluation of Piperidyl and Pyrrolidyl Benzilates as in Vivo Ligands for Muscarinic Acetylcholine Receptors

  摘要：

  A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K-i values ranged from 0.05 nM to > 100 nM. (R)-N-( 2-Fluoroethyl)-3-piperidyl benzilate (3-FEPB, 22, K-i = 12.1 nM) and N-(2-fluoroethyl)-4-piperidyl benzilate (4-FEPB, 8, K-i = 1.83 nM) were selected for radiolabeling with fluorine-18. Using alkylation with 2-[F-18]fluoroethyl triflate, 3-[F-18]FEPB (42) and 4-[F-18]-FEPB (43) were produced in 7-9% radiochemical yield and >97% radiochemical purity. For in vivo studies, retention was moderate in mouse brain for 42; however, blocking with scopolamine showed that uptake was not muscarinic cholinergic receptor-mediated. Conversely, 43 exhibited high, receptor-mediated retention in mouse brain, with significant; clearance after 1 h. These results suggest that 43 could have applications as an in vivo probe for measuring endogenous acetylcholine levels.

  DOI：

  10.1021/jm000305o

文献信息

• Organic compounds
  申请人：Collingwood Paul Stephen

  公开号：US20060287362A1

  公开（公告）日：2006-12-21

  Compounds of formula I in salt or zwitterionic form wherein, wherein R 1 , R 2 , R 3 , R 4 , R 5 , J, L and M have the meanings as indicated in the specification, are useful for treating conditions that are mediated by the muscarinic M3 receptor. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.

  化合物I的盐或双离子形式，其中R1、R2、R3、R4、R5、J、L和M的含义如规范中所示，可用于治疗由肌肉型M3受体介导的疾病。还描述了含有这些化合物的制药组合物和制备这些化合物的过程。
• Piperidinium and pyrrolidinium derivatives as ligands for the muscarinic M3 receptor
  申请人：Novartis AG

  公开号：US07947730B2

  公开（公告）日：2011-05-24

  Compounds of formula I in salt or zwitterionic form wherein, wherein R1, R2, R3, R4, R5, J, L and M have the meanings as indicated in the specification, are useful for treating conditions that are mediated by the muscarinic M3 receptor. Pharmaceutical compositions that contain the compounds and a process for preparing the compounds are also described.

  公式I的化合物以盐或双离子形式存在，其中R1、R2、R3、R4、R5、J、L和M的含义如规范中所示，可用于治疗由肌动蛋白M3受体介导的疾病。还描述了包含该化合物的制药组合物以及制备该化合物的过程。
• 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。
• 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.
• [EN] PIPERIDINIUM AND PYRROLIDINIUM DERIVATIVES AS LIGANDS FOR THE MUSCARINIC M3 RECEPTOR<br/>[FR] COMPOSES ORGANIQUES
  申请人：NOVARTIS AG

  公开号：WO2005000815A3

  公开（公告）日：2005-04-14