BAY 73-6691

BAY 73-6691 is a drug developed by Bayer for the treatment of Alzheimer's disease. It was the first compound developed that acts as a phosphodiesterase inhibitor selective for the PDE9A subtype. The PDE9A enzyme is expressed primarily in the brain, with high concentrations in the cerebellum, neocortex, striatum, and hippocampus, and acts to limit the cGMP-mediated signal transduction which occurs following glutamate binding to NMDA receptors. Consequently, selective PDE9A inhibitors were predicted to prolong intracellular responses to glutamate and enhance glutamate signalling, and since this process is known to be involved in learning and memory, PDE9A inhibitors should have a nootropic effect and may be useful in the treatment of Alzheimer's.[1]

BAY 73-6691
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • 1-(2-Chlorophenyl)-6-[(2R)-3,3,3-trifluoro-2-methylpropyl]-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
ECHA InfoCard100.150.853
Chemical and physical data
FormulaC15H12ClF3N4O
Molar mass356.73 g·mol−1
3D model (JSmol)
SMILES
  • C[C@H](CC1=NC(=O)C2=CNN(C2=N1)C3=CC=CC=C3Cl)C(F)(F)F
InChI
  • InChI=1S/C15H12ClF3N4O/c1-8(15(17,18)19)6-12-21-13-9(14(24)22-12)7-20-23(13)11-5-3-2-4-10(11)16/h2-5,7-8H,6H2,1H3,(H,21,22,24)/t8-/m1/s1 Y
  • Key:FFPXPXOAFQCNBS-MRVPVSSYSA-N Y
 NY (what is this?)  (verify)

Animal studies have confirmed these expectations, and BAY 73-6691 has been shown to improve learning and memory in rats.[2] As the first selective PDE9A inhibitor to be developed, it is also widely used in research into the function of this enzyme subtype. However pre-clinical research is at an early stage and it is not yet known whether BAY 73-6691 will prove suitable to progress to human trials, or if it will remain merely a laboratory research tool.

References
  1. Wunder F, Tersteegen A, Rebmann A, Erb C, Fahrig T, Hendrix M (December 2005). "Characterization of the first potent and selective PDE9 inhibitor using a cGMP reporter cell line". Molecular Pharmacology. 68 (6): 1775–81. doi:10.1124/mol.105.017608. PMID 16150925. S2CID 2054966.
  2. van der Staay FJ, Rutten K, Bärfacker L, Devry J, Erb C, Heckroth H, et al. (October 2008). "The novel selective PDE9 inhibitor BAY 73-6691 improves learning and memory in rodents". Neuropharmacology. 55 (5): 908–18. doi:10.1016/j.neuropharm.2008.07.005. hdl:1874/32084. PMID 18674549. S2CID 24171186.
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