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 PracittoKyle C WilcoxMarcel LindemannJie TongChao ZhengSongye LiSjoerd J FinnemaYiyun HuangZhengxin CaiPublished in: ACS omega (2021)
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.
Keyphrases
- positron emission tomography
- structure activity relationship
- computed tomography
- pet ct
- molecular docking
- high resolution
- pet imaging
- magnetic resonance imaging
- protein protein
- amino acid
- image quality
- binding protein
- contrast enhanced
- small molecule
- molecular dynamics
- magnetic resonance
- mass spectrometry
- high speed
- single molecule