DPA-714

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]

DPA-714
Identifiers
  • N,N-diethyl-2-[4-(2-fluoroethoxy)phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide
CAS Number
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC22H27FN4O2
Molar mass398.482 g·mol−1
3D model (JSmol)
  • CCN(CC)C(=O)Cc1c(nn2c1nc(cc2C)C)c3ccc(cc3)OCCF
  • InChI=1S/C22H27FN4O2/c1-5-26(6-2)20(28)14-19-21(17-7-9-18(10-8-17)29-12-11-23)25-27-16(4)13-15(3)24-22(19)27/h7-10,13H,5-6,11-12,14H2,1-4H3
  • Key:FLZZFWBNYJNHMY-UHFFFAOYSA-N

The binding affinity of DPA-714 for TSPO is reported as Ki = 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

References
  1. Reynolds A, Hanani R, Hibbs D, Damont A, Da Pozzo E, Selleri S, Dollé F, Martini C, Kassiou M (October 2010). "Pyrazolo[1,5-a]pyrimidine acetamides: 4-Phenyl alkyl ether derivatives as potent ligands for the 18 kDa translocator protein (TSPO)". Bioorg. Med. Chem. Lett. 20 (19): 5799–802. doi:10.1016/j.bmcl.2010.07.135. PMID 20727749.
  2. Banister, S. D.; Wilkinson, S. M.; Hanani, R.; Reynolds, A. J.; Hibbs, D. E.; Kassiou, M. (2012). "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. doi:10.1016/j.tetlet.2012.05.044.
  3. James ML, Fulton RR, Vercoullie J, Henderson DJ, Garreau L, Chalon S, Dolle F, Costa B, Selleri S, Guilloteau D, Kassiou M (May 2008). "DPA-714, a new translocator protein-specific ligand: synthesis, radiofluorination, and pharmacologic characterization". J. Nucl. Med. 49 (5): 814–22. doi:10.2967/jnumed.107.046151. PMID 18413395.
  4. Damont A, Hinnen F, Kuhnast B, Schöllhorn-Peyronneau MA, James M, Luus C, Tavitian B, Kassiou M, Dollé F (2008). "Radiosynthesis of [18F]DPA-714, a selective radioligand for imaging the translocator protein (18 kDa) with PET". Journal of Labelled Compounds and Radiopharmaceuticals. 51 (7): 286–292. doi:10.1002/jlcr.1523.
  5. Leaver KR, Reynolds A, Bodard S, Guilloteau D, Chalon S, Kassiou M (2011). "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. doi:10.1021/cn200099e. PMC 3369788. PMID 22860181.


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