The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: The influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents

Eibl, Christoph; Tomassoli, Isabelle; Munoz, Lenka; Stokes, Clare; Papke, Roger L.; Gündisch, Daniela

doi:10.1016/j.bmc.2013.09.059

Cited by 13 publications

(7 citation statements)

References 57 publications

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“…Therefore, we replaced the cationic center with alternative tertiary amine motifs. Insertion of three different diazabicycloalkanes resulted in N -methyl-substituted derivatives of the ethylene- and propylene-bridged piperazines diazabicyclo[3.2.1]octane and diazabicyclo[3.3.1]nonane, respectively [22,23].…”

Section: Introductionmentioning

confidence: 99%

A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand

et al. 2015

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Changes in the expression of α7 nicotinic acetylcholine receptors (α7 nAChRs) in the human brain are widely assumed to be associated with neurological and neurooncological processes. Investigation of these receptors in vivo depends on the availability of imaging OPEN ACCESSMolecules 2015, 20 18388 agents such as radioactively labelled ligands applicable in positron emission tomography (PET). We report on a series of new ligands for α7 nAChRs designed by the combination of dibenzothiophene dioxide as a novel hydrogen bond acceptor functionality with diazabicyclononane as an established cationic center. To assess the structure-activity relationship (SAR) of this new basic structure, we further modified the cationic center systematically by introduction of three different piperazine-based scaffolds. Based on in vitro binding affinity and selectivity, assessed by radioligand displacement studies at different rat and human nAChR subtypes and at the structurally related human 5-HT3 receptor, we selected the compound 7-(1,4-diazabicyclo

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Section: Introductionmentioning

confidence: 99%

A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand

et al. 2015

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“…The diazabicyclic system bispidine was prepared using our published method. 50,51 Subsequent removal of the N- t boc-protecting group by HCl in dioxane led to the desired products. The highest purity (95–99%) was obtained when purified on preparative HPLC using a gradient of MeOH/H 2 O.…”

Section: Resultsmentioning

confidence: 99%

The twin drug approach for novel nicotinic acetylcholine receptor ligands

Tomassoli

Gündisch

2015

Bioorganic & Medicinal Chemistry

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The association of two pharmacophoric entities generates so-called “twin drugs” or dimer derivatives. We applied this approach for the design of a small compound library for the interaction with α4β2* nicotinic acetylcholine receptors (nAChRs). In this compound series, the nAChR ligand N,N-dimethyl-2-(pyridin-3-yloxy)ethan-1-amine 9 served as one pharmacological entity and it was initially kept constant as one part of the “twin” compound. “Twin” compounds with identical or non-identical entities using the “no linker mode” or “overlap” mode were synthesized and evaluated for their nAChR affinities. Compound 17a showed the highest affinity for the α4β2* nAChR subtype (Ki = 0.188 nM) and its (di)fluoro analogs could retain nanomolar affinities, when replacing pyridine as the hydrogen bond acceptor system by mono- or difluoro-phenyls. The “twin drug” approach proved to provide compounds with high affinity and subtype selectivity for α4β2* nAChRs.

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“…mide in 1,2-dichloroethane (DCE) resulting in tautomerization to the respective imine. 36 The subsequent NaBH 4 reduction set the relative configuration at carbon atom C10a and delivered piperidine 25 as a single diastereoisomer (Scheme 5).…”

Section: Paper Synthesismentioning

confidence: 99%

Synthetic Studies towards Pyrido[1,2-a]azepine Stemona Alkaloids

et al. 2022

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The carbon skeleton of the Stemona alkaloids stemokerrin and cochinchistemonine was assembled from three building blocks (a piperidine, a furan, and a tetronate). Key steps linking the fragments included a Stille cross-coupling (piperidine/furan) and an aldol type addition of a tetronate. The furan served as a latent 1,4-difunctional compound which was converted to a γ-ketolactone by a type II photooxygenation. Attempts to construct the C12-C13 double bond of stemokerrin by a late stage oxidation or by an elimination remained unsuccessful. The non-natural products dihydrostemokerrin and furostemokerrin were obtained instead.

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The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor (nAChR) ligands. Part 1: The influence of different hydrogen bond acceptor systems on alkyl and (hetero)aryl substituents

Cited by 13 publications

References 57 publications

A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand

A Promising PET Tracer for Imaging of α7 Nicotinic Acetylcholine Receptors in the Brain: Design, Synthesis, and in Vivo Evaluation of a Dibenzothiophene-Based Radioligand

The twin drug approach for novel nicotinic acetylcholine receptor ligands

Synthetic Studies towards Pyrido[1,2-a]azepine Stemona Alkaloids

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