Synthesis and radioligand binding studies of bis-(8-isopropyl-isoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels

Badarau, Eduard; Dilly, Sébastien; Dufour, Fabien; Poncin, Sylvie; Seutin, Vincent; Liégeois, Jean-François

doi:10.1016/j.bmcl.2011.09.043

Cited by 6 publications

(4 citation statements)

References 19 publications

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“…was used [1]. This strongly reduced the possibility of a sequential process leading to the formation of intermediates which could influence the observed stereoselectivity.…”

Section: Resultsmentioning

confidence: 99%

“…The chemical reduction of the isoquinolinium ring was carried out to obtain similarly THIQ analogues (Scheme 1) [1]. Chiral HPLC conditions previously used [3] did not permit to resolve the isopropyl derivative mixtures.…”

Section: Introductionmentioning

confidence: 99%

“…In our program dedicated to the development of selective modulators of small-conductance calcium-activated potassium (SK) channel subtypes [1,2], isoquinolinium compounds ( Fig. 1 are subsequently transformed to 1,2,3,4-tetrahydroisoquinoline (THIQ) analogues by using sodium borohydride in excess leading to a diastereoisomeric mixture (Scheme 1) in order to obtain potential CNS-penetrating agents [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

“…Bis-isoquinolinium derivatives with significant affinity for SK channels: methoxy (series A)[2] and isopropyl (series B)[1] analogues.…”

mentioning

confidence: 99%

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Structural analysis of some bis-(8-isopropyl-isoquinolinium) derivatives reveals a preferential folded conformation leading to a stereoselective attack by sodium borohydride

Dilly¹,

Badarau²,

Dufour³

et al. 2014

Journal of Molecular Structure

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“…was used [1]. This strongly reduced the possibility of a sequential process leading to the formation of intermediates which could influence the observed stereoselectivity.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Bis-isoquinolinium derivatives with significant affinity for SK channels: methoxy (series A)[2] and isopropyl (series B)[1] analogues.…”

mentioning

confidence: 99%

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Structural analysis of some bis-(8-isopropyl-isoquinolinium) derivatives reveals a preferential folded conformation leading to a stereoselective attack by sodium borohydride

Dilly¹,

Badarau²,

Dufour³

et al. 2014

Journal of Molecular Structure

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Bis‐(1,2,3,4‐tetrahydroisoquinolinium): A Chiral Scaffold for Developing High‐Affinity Ligands for SK Channels

2014

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N-Methyl-bis-(1,2,3,4-tetrahydroisoquinolinium) analogues derived from AG525 (1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2- methyl-1,2,3,4-tetrahydroisoquinoline)) stereoisomers and tetrandrine, a rigid bis-(1,2,3,4-tetrahydroisoquinoline) analogue with an S,S configuration, were synthesized and tested for their affinity for small-conductance calcium-activated potassium channel (SK/KCa2) subtypes using radioligand binding assays. A significant increase in affinity was observed for the quaternized analogues over the parent 1,2,3,4-tetrahydroisoquinoline compounds. Interestingly, the impact of stereochemistry was not the same in the two groups of compounds. For quaternized analogues, affinities of S,S and R,R isomers for SK2 and SK3 channels were similar and in both cases higher than that of the meso derivative. Among the bis-tetrahydroisoquinoline compounds, the S,S isomers exhibited high affinity, while the R,R and meso isomers had similarly lower affinities. Furthermore, the SK2/SK3 selectivity ratio was slightly increased for quaternized analogues. Bis-(1,2,3,4-tetrahydroisoquinolinium) represents a new scaffold for the development of high-affinity ligands for SK channel subtypes.

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Chemical modifications of the N -methyl-laudanosine scaffold point to new directions for SK channels exploration

Badarau

Dilly

Seutin

et al. 2014

Bioorganic & Medicinal Chemistry Letters

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Synthesis and radioligand binding studies of bis-(8-isopropyl-isoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels

Cited by 6 publications

References 19 publications

Structural analysis of some bis-(8-isopropyl-isoquinolinium) derivatives reveals a preferential folded conformation leading to a stereoselective attack by sodium borohydride

Structural analysis of some bis-(8-isopropyl-isoquinolinium) derivatives reveals a preferential folded conformation leading to a stereoselective attack by sodium borohydride

Bis‐(1,2,3,4‐tetrahydroisoquinolinium): A Chiral Scaffold for Developing High‐Affinity Ligands for SK Channels

Chemical modifications of the N -methyl-laudanosine scaffold point to new directions for SK channels exploration

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