DPA-714 explained

DPA-714 or N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-''a'']pyrimidine-3-acetamide is a selective ligand for the translocator protein (TSPO) currently under evaluation for several clinical applications.^[1] For this reason, a practical, multigram synthetic route for its preparation has been described.^[2]

The binding affinity of DPA-714 for TSPO is reported as K_i = 7.0 ± 0.4 nM.^{[3] [4]}

[¹⁸F]DPA-714 is currently under investigation as a potential radiopharmaceutical for imaging TSPO in living systems using positron emission tomography (PET). DPA-714, along with other members of the DPA class of TSPO ligands, has been shown to decrease microglial activation and increase neuronal survival in a quinolinic acid rat model of excitotoxic neurodegeneration, suggesting potential neuroprotective effects.^[5]

See also

• DPA-713

Notes and References

1. Reynolds A, Hanani R, Hibbs D, Damont A, Da Pozzo E, Selleri S, Dollé F, Martini C, Kassiou M . 6 . Pyrazolo[1,5-a]pyrimidine acetamides: 4-Phenyl alkyl ether derivatives as potent ligands for the 18 kDa translocator protein (TSPO) . Bioorganic & Medicinal Chemistry Letters . 20 . 19 . 5799–5802 . October 2010 . 20727749 . 10.1016/j.bmcl.2010.07.135 .
2. Banister SD, Wilkinson SM, Hanani R, Reynolds AJ, Hibbs DE, Kassiou M . 10.1016/j.tetlet.2012.05.044 . A practical, multigram synthesis of the 2-(2-(4-alkoxyphenyl)-5,7-dimethylpyrazolo[1,5-''a'']pyrimidin-3-yl)acetamide (DPA) class of high affinity translocator protein (TSPO) ligands . Tetrahedron Letters . 53 . 29 . 3780–3783 . 2012 .
3. James ML, Fulton RR, Vercoullie J, Henderson DJ, Garreau L, Chalon S, Dolle F, Costa B, Guilloteau D, Kassiou M . 6 . DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization . Journal of Nuclear Medicine . 49 . 5 . 814–822 . May 2008 . 18413395 . 10.2967/jnumed.107.046151 . free .
4. Damont A, Hinnen F, Kuhnast B, Schöllhorn-Peyronneau MA, James M, Luus C, Tavitian B, Kassiou M, Dollé F . Radiosynthesis of [¹⁸F]DPA-714, a selective radioligand for imaging the translocator protein (18 kDa) with PET . 51 . 7 . 286–292 . 2008 . 10.1002/jlcr.1523 . Journal of Labelled Compounds and Radiopharmaceuticals.
5. Leaver KR, Reynolds A, Bodard S, Guilloteau D, Chalon S, Kassiou M . Effects of translocator protein (18 kDa) ligands on microglial activation and neuronal death in the quinolinic-acid-injected rat striatum . ACS Chemical Neuroscience . 3 . 2 . 114–119 . February 2012 . 22860181 . 3369788 . 10.1021/cn200099e .