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

Richard Pracitto; Kyle C Wilcox; Marcel Lindemann; Jie Tong; Chao Zheng; Songye Li; Sjoerd J Finnema; Yiyun Huang; Zhengxin Cai

doi:10.1021/acsomega.1c02433

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

ACS Omega. 2021 Oct 8;6(42):27676-27683. doi: 10.1021/acsomega.1c02433. eCollection 2021 Oct 26.

Authors

Richard Pracitto¹, Kyle C Wilcox², Marcel Lindemann¹, Jie Tong¹, Chao Zheng¹, Songye Li¹, Sjoerd J Finnema^{1

2}, Yiyun Huang¹, Zhengxin Cai¹

Affiliations

¹ PET Center, Yale University School of Medicine, New Haven, Connecticut 06520, United States.
² Translational Imaging Neuroscience, AbbVie, North Chicago, Illinois 60064, United States.

Abstract

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.

Grants and funding

UL1 TR001863/TR/NCATS NIH HHS/United States