Cargando…

Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones

[Image: see text] A series of synaptic vesicle protein 2A (SV2A) ligands were synthesized to explore the structure–activity relationship and to help further investigate a hydrogen bonding pharmacophore hypothesis. Racemic SynVesT-1 was used as a lead compound to explore the replacement of the 3-meth...

Descripción completa

Detalles Bibliográficos
Autores principales: Pracitto, Richard, Wilcox, Kyle C., Lindemann, Marcel, Tong, Jie, Zheng, Chao, Li, Songye, Finnema, Sjoerd J., Huang, Yiyun, Cai, Zhengxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552234/
https://www.ncbi.nlm.nih.gov/pubmed/34722967
http://dx.doi.org/10.1021/acsomega.1c02433
_version_ 1784591333291196416
author Pracitto, Richard
Wilcox, Kyle C.
Lindemann, Marcel
Tong, Jie
Zheng, Chao
Li, Songye
Finnema, Sjoerd J.
Huang, Yiyun
Cai, Zhengxin
author_facet Pracitto, Richard
Wilcox, Kyle C.
Lindemann, Marcel
Tong, Jie
Zheng, Chao
Li, Songye
Finnema, Sjoerd J.
Huang, Yiyun
Cai, Zhengxin
author_sort Pracitto, Richard
collection PubMed
description [Image: see text] A series of synaptic vesicle protein 2A (SV2A) ligands were synthesized to explore the structure–activity relationship and to help further investigate a hydrogen bonding pharmacophore hypothesis. Racemic SynVesT-1 was used as a lead compound to explore the replacement of the 3-methyl group on the pyridinyl moiety with halogens and hydrocarbons. Pyridinyl isomers of racemic SynVesT-1 were also investigated. Highly potent analogs were discovered including a 3-iodo pyridinyl ligand amenable to investigation as a PET or SPECT imaging agent.
format Online
Article
Text
id pubmed-8552234
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-85522342021-10-29 Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones Pracitto, Richard Wilcox, Kyle C. Lindemann, Marcel Tong, Jie Zheng, Chao Li, Songye Finnema, Sjoerd J. Huang, Yiyun Cai, Zhengxin ACS Omega [Image: see text] A series of synaptic vesicle protein 2A (SV2A) ligands were synthesized to explore the structure–activity relationship and to help further investigate a hydrogen bonding pharmacophore hypothesis. Racemic SynVesT-1 was used as a lead compound to explore the replacement of the 3-methyl group on the pyridinyl moiety with halogens and hydrocarbons. Pyridinyl isomers of racemic SynVesT-1 were also investigated. Highly potent analogs were discovered including a 3-iodo pyridinyl ligand amenable to investigation as a PET or SPECT imaging agent. American Chemical Society 2021-10-08 /pmc/articles/PMC8552234/ /pubmed/34722967 http://dx.doi.org/10.1021/acsomega.1c02433 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Pracitto, Richard
Wilcox, Kyle C.
Lindemann, Marcel
Tong, Jie
Zheng, Chao
Li, Songye
Finnema, Sjoerd J.
Huang, Yiyun
Cai, Zhengxin
Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones
title Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones
title_full Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones
title_fullStr Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones
title_full_unstemmed Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones
title_short Further Investigation of Synaptic Vesicle Protein 2A (SV2A) Ligands Designed for Positron Emission Tomography and Single-Photon Emission Computed Tomography Imaging: Synthesis and Structure–Activity Relationship of Substituted Pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones
title_sort further investigation of synaptic vesicle protein 2a (sv2a) ligands designed for positron emission tomography and single-photon emission computed tomography imaging: synthesis and structure–activity relationship of substituted pyridinylmethyl-4-(3,5-difluorophenyl)pyrrolidin-2-ones
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552234/
https://www.ncbi.nlm.nih.gov/pubmed/34722967
http://dx.doi.org/10.1021/acsomega.1c02433
work_keys_str_mv AT pracittorichard furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT wilcoxkylec furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT lindemannmarcel furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT tongjie furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT zhengchao furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT lisongye furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT finnemasjoerdj furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT huangyiyun furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones
AT caizhengxin furtherinvestigationofsynapticvesicleprotein2asv2aligandsdesignedforpositronemissiontomographyandsinglephotonemissioncomputedtomographyimagingsynthesisandstructureactivityrelationshipofsubstitutedpyridinylmethyl435difluorophenylpyrrolidin2ones