Synthesis and in vitro evaluation of 5-substituted benzovesamicol analogs containing N-substituted amides as potential positron emission tomography tracers for the vesicular acetylcholine transporter

Roslin, Sara; Rosa, Maria de Lurdes Pereira; Deuther‐Conrad, Winnie; Eriksson, Jonas; Odell, Luke R.; Antoni, Gunnar; Brust, Peter; Larhed, Mats

doi:10.1016/j.bmc.2017.01.041

Cited by 5 publications

(3 citation statements)

References 52 publications

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“…Scheme 14 Selected examples of biologically relevant target compounds synthesized by Mo(CO) 6 -mediated alkoxy-or aminocarbonylation. References: VACht, 86 kinase, 87 AT 2 R, 88 ghrelin, 89 (±)-ampelopsin B, 90 CDK8, 91 neurotensin, 92 α3β4 nAChR ligand 93 All of the examples described in the preceding pages have been conducted under a homogenous catalysis regime. Despite its immense popularity and utility, homogeneous catalysis suffers from two major drawbacks.…”

Section: Account Syn Lettmentioning

confidence: 99%

Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions

Åkerbladh

Odell

Larhed

2018

Synlett

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This account summarizes Pd(0)-catalyzed Mo(CO)6-mediated gas-free carbonylative reactions published in the period October 2011 to May 2018. Presented reactions include inter- and intramolecular carbonylations, carbonylative cross-couplings, and carbonylative multicomponent reactions using Mo(CO)6 as a solid source of CO. The presented methodologies were developed mainly for small-scale applications, avoiding the problematic use of gaseous CO in a standard laboratory. In most cases, the reported Mo(CO)6-mediated carbonylations were conducted in sealed vials or by using two-chamber solutions.1 Introduction2 Recent Developments2.1 New CO Sources2.2 Two-Chamber System for ex Situ CO Generation2.3 Multicomponent Carbonylations3 Carbonylations with N and O Nucleophiles4 Carbonylative Cross-Coupling Reactions with Organometallics5 Carbonylative Cascade Reactions6 Carbonylative Cascade, Multistep Reactions7 Summary and Outlook

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Section: Account Syn Lettmentioning

confidence: 99%

Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions

Åkerbladh

Odell

Larhed

2018

Synlett

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“…39 VAChT is a transmembrane protein expressed in cholinergic neurons in CNS and located on presynaptic vesicles of cholinergic neurons. VAChT transports the neurotransmitter ACh into the vesicles for storage and release, thus being is a key feature in the cholinergic neurotransmission 40 and an important target for in vivo imaging of neurodegenerative diseaes, such AD, 41 using positron emission tomography (PET). On the other hand, vesamicol, a well-known VAChT PET radioligand, produces a noncompetitive and reversible block of VAChT responsible for carrying newly synthesized ACh into secretory vesicles, decreasing ACh release.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Contilisant, a Tetratarget Small Molecule for Alzheimer’s Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile

et al. 2018

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Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecular modeling. In addition, contilisant significantly restores the cognitive deficit induced by Aβ in the radial maze assay in an in vivo Alzheimer's disease test, comparing very favorably with donepezil.

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“…The minute amounts of [ 11 C]CO available for reaction and the requisite for a finished synthesis within 2–3 half-lives of carbon-11 set the framework for a transition-metal-mediated 11 C-carbonylation. We have previously used the xenon system for ambient pressure carbonylations and demonstrated its feasibility in synthesising amides [ 53 , 54 ] and sulfonyl carbamates [ 55 ]. The report by Kealey et al as well as our own observations that 11 C-labelled ureas can form as byproducts in the synthesis of 11 C-labelled amides, especially when a Pd(II) source is used as a pre-catalyst for the aminocarbonylation, sparked our interest in exploring the Pd(II)-mediated formation of 11 C-labelled ureas [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 11C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation

et al. 2017

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Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [11C]carbon monoxide. Starting with amines and [11C]carbon monoxide, both symmetrical and unsymmetrical 11C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [11C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/μmol–319 GBq/μmol). DFT calculations were found to support a reaction mechanism proceeding through an 11C-labelled isocyanate intermediate.

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Synthesis and in vitro evaluation of 5-substituted benzovesamicol analogs containing N-substituted amides as potential positron emission tomography tracers for the vesicular acetylcholine transporter

Cited by 5 publications

References 52 publications

Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions

Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions

Contilisant, a Tetratarget Small Molecule for Alzheimer’s Disease Therapy Combining Cholinesterase, Monoamine Oxidase Inhibition, and H3R Antagonism with S1R Agonism Profile

Synthesis of 11C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation

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