[6-chloro-3-pyridylmethyl-3H] neonicotinoids as high-affinity radioligands for the nicotinic acetylcholine receptor: Preparation using NaB3H4 and LiB3H4

Latli, Bachir; Than, Chit; Morimoto, Hiromi; Williams, Philip G.; Casida, John E.

doi:10.1002/(sici)1099-1344(199611)38:11<971::aid-jlcr923>3.0.co;2-u

Cited by 28 publications

(13 citation statements)

References 16 publications

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“…17 Modifications of Heterocyclic Amine and Trialkylammonium Moieties of 6-Chloro-3-pyridinylScheme 1. Synthesis of 6-Chloro-3-pyridinylmethyl Ligands with Modifications in the Heterocyclic Imine Moiety (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) or Related Compounds (11)(12)(13)(14) methyl Ligands 18-23 (Scheme 2). The azetidine derivative 18 was prepared by coupling CCMP to 3-chloropropylamine in the usual manner, followed by cyclization in refluxing acetonitrile.…”

Section: Resultsmentioning

confidence: 99%

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Novel and Potent 6-Chloro-3-pyridinyl Ligands for the α4β2 Neuronal Nicotinic Acetylcholine Receptor

Latli

D’Amour

1999

J. Med. Chem.

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1-[(6-Chloro-3-pyridinyl)methyl]-2-imidazolidine (1), the N-desnitro metabolite of the major insecticide imidacloprid, is known to have similar potency to that of (-)-nicotine as an inhibitor of [3H](-)-nicotine binding at the rat recombinant alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR); IC50 values in the present study are 3.8 nM for (-)-nicotine, 6.0 nM for 1, and 155 nM for imidacloprid. Synthesis of new analogues of 1, modified only in the heterocyclic moiety (five-, six-, or seven-membered rings with NH, S, O, and CH2 substituents), gave compounds varying from 4-fold higher potency (2-iminothiazole analogue 10) to >6000-fold less active than (-)-nicotine. Other potent N-[(6-chloro-3-pyridinyl)methyl] compounds are those in which the heterocyclic imine is replaced with pyrrolidine (19) (IC50 9 nM) or trimethylammonium (22) (IC50 18 nM). A novel conversion of (-)-nicotine to its 6-chloro analogue increased the potency 2-fold. These 6-chloro-3-pyridinyl compounds are of interest as novel nAChR probes and potential metabolites of candidate insecticides.

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Section: Resultsmentioning

confidence: 99%

“…Each compound was >98% pure based on TLC and 1 H and 13 C NMR integrations.1-[(6-Chloro-3-pyridinyl)methyl]-2-iminoimidazolidine (1). Prepared as before 14. 1-[(6-Chloro-3-pyridinyl)methyl]-1,3-diaminopropane.…”

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confidence: 99%

Novel and Potent 6-Chloro-3-pyridinyl Ligands for the α4β2 Neuronal Nicotinic Acetylcholine Receptor

Latli

D’Amour

1999

J. Med. Chem.

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“…The radiosynthesis of tritium‐labeled 2‐chloro‐5‐((2‐(nitromethylene) imidazolidin‐1‐yl)methyl)pyridine (6‐Cl‐PMNI) (Figure 1) has been reported by Latli et al ,9 which involves high specific activity NaB 3 H 4 and a multi‐step microsynthesis. It required microreactor and difficult operation to achieve the final resolution.…”

Section: Resultsmentioning

confidence: 96%

Radiosynthesis of tritium-labeled novel nitromethylene neonicotinoids compounds with NaB3H4

et al. 2011

J Label Compd Radiopharm

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“…Reduction of the respective carboxylic acid halides 229 and 231 gave the respective [a,a-3 H 2 ]carbinols; subsequent conversion of them to the corresponding benzyl halides and halide displacements with nitrogen-and sulfur nucleophiles afforded, respectively, the insecticidal N-acetylcholinesterase inhibitor [ 3 H 2 ]CH-IMI (230) 214 and the photoaffinity probe (trifluoromethyl)diazirinyl[S-methylene-3 H 2 ]pyridaben (232) 215 in 30-50% radiochemical yields and at specific activities in the range of 55-56 Ci/mmol. Reduction of the respective carboxylic acid halides 229 and 231 gave the respective [a,a-3 H 2 ]carbinols; subsequent conversion of them to the corresponding benzyl halides and halide displacements with nitrogen-and sulfur nucleophiles afforded, respectively, the insecticidal N-acetylcholinesterase inhibitor [ 3 H 2 ]CH-IMI (230) 214 and the photoaffinity probe (trifluoromethyl)diazirinyl[S-methylene-3 H 2 ]pyridaben (232) 215 in 30-50% radiochemical yields and at specific activities in the range of 55-56 Ci/mmol.…”

Section: I-bu 2 Alclmentioning

confidence: 99%

Preparation of Tritium‐Labeled Compounds by Chemical Synthesis

2009

Preparation of Compounds Labeled With Tritium and Carbon‐14

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In contrast to isotope exchange methods, which utilize the target compound or a late intermediate as substrate for labeling, chemical synthesis involves transformation of some precursor chemical with concurrent introduction of tritium. Four basic types of transformations are distinguished for discussion each in turn. They are catalytic tritiations (Section 4.1), which usually involve the reduction of a precursor compound using a catalyst and tritium gas; catalytic tritiolyses (Section 4.2), involving the replacement of functional groups by tritium, again using a catalyst and tritium gas; tritide reductions (Section 4.3), utilizing tritiated versions of hydridic reducing reagents; and the use of small tritiated building blocks (Section 4.4) in synthetic operations to construct target molecules.A phenomenon strongly relevant to the catalytic methods discussed in Sections 4.1 and 4.2, and of some relevance also for tritide chemistry (Section 4.3) is solvent exchange. Most catalytic tritiations and tritiolyses are conducted in solution, and a wide variety of solvents have been used, ranging from nonpolar ones to highly polar, hydroxylic media. The properties of the solvent, however, influence not only the course and rate of a heterogeneously catalyzed reaction, but also the extent to which solvent hydrogen may exchange with tritium gas as a side reaction and thereby dilute the isotope introduced into the substrate: solvent exchange. It is commonly recognized that the use of protic solvents for tritiations and tritiolyses increases the risk of obtaining products of less than maximal specific activity, although it is equally clear that such reactions often succeed without dilution of label. The crucial factor in each experiment is the relationship between the rate of the tritium-incorporation reaction and the rate(s) of any tritium-diluting reaction(s). It is documented that the rate of metal-catalyzed exchange between elemental hydrogen and water is significant, especially at low pH 1 , but little quantitative data are available to guide practice. Recently a turnover number of 17.3 h À1 was reported for the exchange between H 2 and 2 H 2 O catalyzed by 10% Pd/C at room temperature and a pressure of 1 atm 2 ; this is rapid enough to provide the basis for an economical method of catalytic deuterium exchange Preparation of Compounds Labeled with Tritium and Carbon-14 Rolf Voges, J. Richard Heys and Thomas Moenius

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[6-chloro-3-pyridylmethyl-3H] neonicotinoids as high-affinity radioligands for the nicotinic acetylcholine receptor: Preparation using NaB3H4 and LiB3H4

Cited by 28 publications

References 16 publications

Novel and Potent 6-Chloro-3-pyridinyl Ligands for the α4β2 Neuronal Nicotinic Acetylcholine Receptor

Novel and Potent 6-Chloro-3-pyridinyl Ligands for the α4β2 Neuronal Nicotinic Acetylcholine Receptor

Radiosynthesis of tritium-labeled novel nitromethylene neonicotinoids compounds with NaB3H4

Preparation of Tritium‐Labeled Compounds by Chemical Synthesis

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