Delving into the Latest Updates on TSPO modulators(National Institute of Radiological Sciences) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Diagnostic radiopharmaceuticals

Synonyms

[ 11C] 3a

Target

TSPO

Action

modulators, enhancers

Mechanism

TSPO modulators(Translocator protein modulators), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Pneumonia

Inactive Indication-

Originator Organization

National Institute of Radiological Sciences

Active Organization

National Institute of Radiological Sciences

Inactive Organization-

License Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

To develop a PET ligand for imaging TSPO in peripheral organs, we designed three novel oxopurine analogues [(11)C]3a-c (LogD: 1.81-2.17) by introducing a pyridine ring in place of a benzene ring in the lead compound [(11)C]2 (LogD: 3.48). The desmethyl precursors 10 for radiosynthesis were synthesized by reacting glycine 7 with picolylamines 4, followed by hydrolysis and by Curtius rearrangement with diphenylphosphoryl azide. Methylation of 10a-c with methyl iodide produced unlabeled compounds 3a-c. The radiosynthesis of [(11)C]3a-c was performed by reacting 10a-c with [(11)C]methyl iodide. Compounds 3a-c displayed high or moderate in vitro binding affinities (K(i): 5-40 nM) for TSPO. PET with [(11)C]3a-c in rats showed high uptake in the lung, heart, and kidney, which are organs with high TSPO expression. Metabolite analysis with [(11)C]3a showed that radioactivity in these organs mainly corresponded with unchanged [(11)C]3a. PET with [(11)C]3a using a rat model of lung inflammation showed a significant signal in the lipopolysaccharide-treated lung.

100 Deals associated with TSPO modulators(National Institute of Radiological Sciences)

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