Synthesis of some Arecaidine Derivatives

Tsukamoto, Takeo; Komori, Tetsuya

doi:10.1248/yakushi1947.73.7_779

Cited by 2 publications

(3 citation statements)

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“…Substitution of 4 a with guvacine ethyl ester (5) [28,29] resulted in ester 6 a from which the dibromo analogue 7 a of NO 711 (1) was obtained upon subsequent hydrolysis. Compound 7 a was then transformed into the final compound [ 3 H 2 ]NO 711 (2) through a catalytic halogen-tritium exchange performed by custom synthesis [30] following the catalytic Wilzbach procedure.…”

Section: Resultsmentioning

confidence: 99%

MS‐Binding Assays: Kinetic, Saturation, and Competitive Experiments Based on Quantitation of Bound Marker as Exemplified by the GABA Transporter mGAT1

2006

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A new kind of binding assay is described in which the amount of a nonlabeled marker bound to the target is quantified by LC-ESI-MS-MS. This new approach was successfully implemented with nonlabeled NO 711 as marker and the GABA transporter subtype mGAT1 as target. The native marker bound to the target was liberated from the receptor protein by methanol denaturation after filtration. A reliable and sensitive LC-ESI-MS-MS method for the quantitation of NO 711 was developed, and data from mass spectrometric detection were analyzed by nonlinear regression. Kinetic MS-binding experiments yielded values for k+1 and k-1, while in saturation MS-binding experiments, Kd and Bmax values were determined. In competitive MS-binding experiments, Ki values were obtained for various test compounds covering a broad range of affinities for mGAT1. All experiments were performed in 96-well plate format with a filter plate for the separation step which improved the efficiency and throughput of the procedure. The method was validated by classical radioligand-binding experiments with the labeled marker [3H2]NO 711 in parallel. The results obtained from MS-binding experiments were found to be in good agreement with the results of the radioligand-binding assays. The new kind of MS-binding assay presented herein is further adapted to the conventional radioligand-binding assay in that the amount of bound marker is securely quantified. This promises easy implementation in accordance with conventional binding assays without the major drawbacks that are inherent in radioligand or fluorescence binding assays. Therefore, MS-binding assays are a true alternative to classical radioligand-binding assays.

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Section: Resultsmentioning

confidence: 99%

MS‐Binding Assays: Kinetic, Saturation, and Competitive Experiments Based on Quantitation of Bound Marker as Exemplified by the GABA Transporter mGAT1

2006

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“…The reaction of bis(4‐bromophenyl)methanone oxime ( 3 a )27 with 1‐bromo‐2‐chloroethane in the presence of K 2 CO 3 provided the oxime ether 4 a . Substitution of 4 a with guvacine ethyl ester ( 5 )28, 29 resulted in ester 6 a from which the dibromo analogue 7 a of NO 711 ( 1 ) was obtained upon subsequent hydrolysis. Compound 7 a was then transformed into the final compound [ 3 H 2 ]NO 711 ( 2 ) through a catalytic halogen–tritium exchange performed by custom synthesis30 following the catalytic Wilzbach procedure.…”

Section: Resultsmentioning

confidence: 99%

“…Ethyl 1‐[2‐({[bis(4‐bromophenyl)methylene]amino}oxy)ethyl]‐1,2,5,6‐tetrahydropyridine‐3‐carboxylate ( 6 a ): Guvacine ethyl ester28, 29 ( 5 ) (300 mg, 1.9 mmol) and dried K 2 CO 3 (520 mg, 3.8 mmol) were added to a solution of 4 a (793 mg, 1.9 mmol) in toluene (25 mL). The reaction mixture was heated at reflux for 120 h. After cooling to room temperature, filtration and evaporation provided a slightly yellow oil which was purified by CC (cyclohexane/EtOAc 9:1, increasing polarity to 1:1).…”

Section: Methodsmentioning

confidence: 99%

Jungchemikerforum

Küchenthal¹

2008

Nachr Chem

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A new kind of binding assay is described in which the amount of a nonlabeled marker bound to the target is quantified by LC–ESI‐MS–MS. This new approach was successfully implemented with nonlabeled NO 711 as marker and the GABA transporter subtype mGAT1 as target. The native marker bound to the target was liberated from the receptor protein by methanol denaturation after filtration. A reliable and sensitive LC–ESI‐MS–MS method for the quantitation of NO 711 was developed, and data from mass spectrometric detection were analyzed by nonlinear regression. Kinetic MS‐binding experiments yielded values for k+1 and k−1, while in saturation MS‐binding experiments, Kd and Bmax values were determined. In competitive MS‐binding experiments, Ki values were obtained for various test compounds covering a broad range of affinities for mGAT1. All experiments were performed in 96‐well plate format with a filter plate for the separation step which improved the efficiency and throughput of the procedure. The method was validated by classical radioligand‐binding experiments with the labeled marker [3H2]NO 711 in parallel. The results obtained from MS‐binding experiments were found to be in good agreement with the results of the radioligand‐binding assays. The new kind of MS‐binding assay presented herein is further adapted to the conventional radioligand‐binding assay in that the amount of bound marker is securely quantified. This promises easy implementation in accordance with conventional binding assays without the major drawbacks that are inherent in radioligand or fluorescence binding assays. Therefore, MS‐binding assays are a true alternative to classical radioligand‐binding assays.

show abstract

Synthesis of some Arecaidine Derivatives

Cited by 2 publications

References 0 publications

MS‐Binding Assays: Kinetic, Saturation, and Competitive Experiments Based on Quantitation of Bound Marker as Exemplified by the GABA Transporter mGAT1

MS‐Binding Assays: Kinetic, Saturation, and Competitive Experiments Based on Quantitation of Bound Marker as Exemplified by the GABA Transporter mGAT1

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