[3H]-(+)-QNB | 62869-68-5

• 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: [3H]-(+)-QNB
• 英文别名: (+)-QNB；Quinuclidinyl benzilate, (+)-；[(3S)-1-azabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-diphenylacetate
• CAS: 62869-68-5
• 化学式: C₂₁H₂₃NO₃
• 分子量: 337.419
• InChiKey: HGMITUYOCPPQLE-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  1-溴-3-苯基丙烷 、 [3H]-(+)-QNB 以 1,4-二氧六环 为溶剂， 反应 48.0h， 以85%的产率得到(S)-(+)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide
  参考文献：
  名称：

  Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity

  摘要：

  The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2] octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(-)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[ 2.2.2] octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM(3)R). Compared to 1 and 5, (R)-(-)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(-)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(-)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.

  DOI：

  10.1016/j.bmc.2019.06.016
• 作为产物：
  描述：

  (S)-(+)-3-喹宁醇 、 1,1-二苯基-1-羟基乙酸乙酯 在 sodium 作用下， 生成 [3H]-(+)-QNB
  参考文献：
  名称：

  苯并3-奎宁环烯基旋光异构体和相关毒蕈碱拮抗剂的亲和性和选择性。

  摘要：

  毒蕈碱拮抗剂3-（1-氮杂双环[2.2.2]辛基）α-羟基-α，α-二苯乙酸酯（3-喹啉基苯甲酸根，QNB，1）3-（1-氮杂双环[2.2。]的所有旋光异构体。 2]辛基）氧杂蒽9-羧酸盐（3-奎宁环烯基氧杂蒽9-羧酸盐，QNX，2）和3-（1-氮杂双环[2.2.2] ocytl）α-羟基-α-苯基丙酸酯（3-奎宁环戊基丙酸酯） ，QNA，3）被制备并在结合和功能测定中研究。在所有情况下，（R）-1-氮杂双环[2.2.2] octan-3-ol（3-quinuclidinol）的酯对毒蕈碱乙酰胆碱受体（M-AChRs）的M1和M2亚群具有更大的亲和力同行。QNB（1），QNX（2）和QNA（3）的对映异构体（其中毒蕈碱拮抗剂的醇部分具有S绝对立体化学）对M1-AChR更具选择性。该选择性是通过性质（在QNA的情况下）是酸部分的手性来调节的。该系列中最有效的异构体是（R）-Q​​NB。在QN

  DOI：

  10.1021/jm00402a035

文献信息

• Highly efficient synthesis of [11C]Me-QNB, a selective radioligand for the quantification of the cardiac muscarinic receptors using PET
  作者：Fr�d�ric Dolle、Fran�oise Hinnen、Fran�oise Vaufrey、St�phane Demphel、Yann Bramoulle、Denis Fournier、Michel Ponchant、H�ric Valette、Christian Crouzel

  DOI：10.1002/jlcr.460

  日期：2001.4

  Me-QNB (N-methyl-quinuclidin-3-yl benzilate or N-methyl-quinuclidin-3-yl diphenylhydroxy acetate) is a hydrophilic, non-metabolized and highly specific muscarinic acetylcholinergic antagonist. Using this quaternary ammonium derivative of QNB, labelled with carbon-11, a positron-emitting isotope (half-life : 20.4 minutes), the potential for quantification of myocardial muscarinic receptors in vivo using the high-resolution, sensitive and quantitative imaging technique PET (positron emission tomography) was previously demonstrated in dogs and validated in humans. In this paper, the radiosynthesis of carbon-11-labelled Me-QNB is investigated and oriented towards the preparation of multi milliCuries of radiotracer. Typically, using no-carrier-added [11C]methyl triflate as the alkylating agent and 0.64 mg (1.89 µmol) of QNB as precursor for labelling at 100°C for 1 minute lead to a 48.5% +/−10% (15 runs) decay-corrected radiochemical yield (based on [11C]methyl triflate). 183 mCi (+/−39) of [11C]Me-QNB ([11C]-1) could be synthesized in only 27 to 28 minutes after EOB and occasionally, up to 340 mCi of [11C]Me-QNB ([11C]-1) were obtained, corresponding to a 85% decay-corrected yield. The associated decay-corrected specific radioactivities obtained were 2658 mCi/µmol (+/−971) at EOB. Copyright © 2001 John Wiley & Sons, Ltd.

  Me-QNB (N-甲基-喹宁环-3-基苄酯或N-甲基-喹宁环-3-基二苯羟乙酸酯)是一种亲水性、非代谢性和高度特异性的毒蕈碱型乙酰胆碱拮抗剂。使用这种标记有碳-11(一种正电子发射同位素，半衰期为20.4分钟)的QNB四级铵衍生物，先前已在狗中证明了利用高分辨率、灵敏和定量的成像技术(正电子发射断层扫描，PET)对心肌毒蕈碱受体进行定量测量的潜力，并在人类中得到了验证。本文研究了碳-11标记的Me-QNB的放射合成，旨在制备多毫居里的放射性示踪剂。通常，使用无载体添加的[11C]甲基三氟甲磺酸酯作为烷基化剂，并以0.64 mg (1.89 µmol)的QNB作为标记前体，在100°C下标记1分钟，得到48.5% ±10%(15次运行)的衰变校正放射化学产率(基于[11C]甲基三氟甲磺酸酯)。在EOB后仅27到28分钟内可以合成183 mCi (±39)的[11C]Me-QNB ([11C]-1)，偶尔可获得高达340 mCi的[11C]Me-QNB ([11C]-1)，对应于85%的衰变校正产率。在EOB时获得的关联衰变校正比活度为2658 mCi/µmol (±971)。版权所有 © 2001 John Wiley & Sons, Ltd.
• RZESZOTARSKI, W. JANUSZ;MCPHERSON, DANIEL W.;FERKANY, JOHN W.;KINNIER, WI+, J. MED. CHEM., 31,(1988) N 7, 1463-1466
  作者：RZESZOTARSKI, W. JANUSZ、MCPHERSON, DANIEL W.、FERKANY, JOHN W.、KINNIER, WI+

  DOI：——

  日期：——
• Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate, a muscarinic receptor antagonist with anti-inflammatory activity
  作者：Yasunobu Yamashita、Ken-ichiro Tanaka、Naoki Yamakawa、Teita Asano、Yuki Kanda、Ayaka Takafuji、Masahiro Kawahara、Mitsuko Takenaga、Yoshifumi Fukunishi、Tohru Mizushima

  DOI：10.1016/j.bmc.2019.06.016

  日期：2019.8

  The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2] octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(-)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[ 2.2.2] octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM(3)R). Compared to 1 and 5, (R)-(-)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(-)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(-)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.
• Affinity and selectivity of the optical isomers of 3-quinuclidinyl benzilate and related muscarinic antagonists
  作者：W. Janusz Rzeszotarski、Daniel W. McPherson、John W. Ferkany、William J. Kinnier、Lalita Noronha-Blob、Alicja Kirkien-Rzeszotarski

  DOI：10.1021/jm00402a035

  日期：1988.7

  All of the optical isomers of the muscarinic antagonists 3-(1-azabicyclo[2.2.2]octyl) alpha-hydroxy-alpha,alpha-diphenylacetate (3-quinuclidinyl benzilate, QNB, 1) 3-(1-azabicyclo[2.2.2]octyl) xanthene-9-carboxylate (3-quinuclidinyl xanthene-9-carboxylate, QNX, 2), and 3-(1-azabicyclo[2.2.2]ocytl) alpha-hydroxy-alpha-phenylpropionate (3-quinuclidinyl atrolactate, QNA, 3) were prepared and studied in

  毒蕈碱拮抗剂3-（1-氮杂双环[2.2.2]辛基）α-羟基-α，α-二苯乙酸酯（3-喹啉基苯甲酸根，QNB，1）3-（1-氮杂双环[2.2。]的所有旋光异构体。 2]辛基）氧杂蒽9-羧酸盐（3-奎宁环烯基氧杂蒽9-羧酸盐，QNX，2）和3-（1-氮杂双环[2.2.2] ocytl）α-羟基-α-苯基丙酸酯（3-奎宁环戊基丙酸酯） ，QNA，3）被制备并在结合和功能测定中研究。在所有情况下，（R）-1-氮杂双环[2.2.2] octan-3-ol（3-quinuclidinol）的酯对毒蕈碱乙酰胆碱受体（M-AChRs）的M1和M2亚群具有更大的亲和力同行。QNB（1），QNX（2）和QNA（3）的对映异构体（其中毒蕈碱拮抗剂的醇部分具有S绝对立体化学）对M1-AChR更具选择性。该选择性是通过性质（在QNA的情况下）是酸部分的手性来调节的。该系列中最有效的异构体是（R）-Q​​NB。在QN