62869-68-5Relevant academic research and scientific papers
Highly efficient synthesis of [11C]Me-QNB, a selective radioligand for the quantification of the cardiac muscarinic receptors using PET
Dolle, Frederic,Hinnen, Francoise,Vaufrey, Francoise,Demphel, Stephane,Bramoulle, Yann,Fournier, Denis,Ponchant, Michel,Valette, Heric,Crouzel, Christian
, p. 337 - 345 (2001)
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.
Affinity and Selectivity of the Optical Isomers of 3-Quinuclidinyl BenzAlate and Related Muscarinic Antagonists
Rzeszotarski, W. Janusz,McPherson, Daniel W.,Ferkany, John W.,Kinnier, William J.,Noronha-Blob, Lalita,Kirkien-Rzeszotarski, Alicja
, p. 1463 - 1466 (2007/10/02)
All the optical isomers of the muscarinic antagonists 3-(1-azabicyclooctyl) α-hydroxy-α,α-diphenylacetate (3-quinuclidinyl benzilate, QNB, 1), 3-(1-azabicyclooctyl)xanthene-9-carboxylate (3-quinuclidinyl xanthene-9-carboxylate, QNX, 2), and 3-(1-azabicyclooctyl) α-hydroxy-α-phenylpropionate (3-quinuclidinyl atrolactate, QNA, 3) were prepared and studied in binding and functional assays.In all instances the esters of (R)-1-azabicyclooctan-3-ol (3-quinuclidinol) had greater affinity for the M1 and M2 subpopulations of muscarinic acetylcholine receptors (M-AChRs) than did their S counterparts.The enantiomers of QNB (1), QNX (2), and QNA (3) in which the alcoholic portion of the muscarinic anatagonists had the S absolute stereochemistry were more selective for the M1-AChRs.This selectivity was modulated by the nature and, in the case of QNA, the chirality of the acid portion.The most potent isomer in the series was (R)-QNB.In the QNA series the diastereoisomer with the absolute R configuration of the alcohol (a) and the R configuration of the acid (b) was the most potent in both binding and functional assays whereas (Sa,Rb)-QNA was the most selective for the M1 subtype of M-AChRs.In fact, the latter diastereomer was as potent and selective as pirenzepine for M1-AChRs.
