Ro4938581

Ro4938581

Identifiers
IUPAC name 3-bromo-10-(difluoromethyl)-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine
PubChem (CID)	11624499
IUPHAR/BPS	4299
ChemSpider	9799246
ChEMBL	CHEMBL1080588
Chemical and physical data
Formula	C13H8BrF2N5
Molar mass	352.14 g/mol
3D model (Jmol)	Interactive image
SMILES FC(F)C(N=C1)=C(N1C2=C3C=C(Br)C=C2)CN4C3=NC=N4
InChI InChI=1S/C13H8BrF2N5/c14-7-1-2-9-8(3-7)13-17-5-19-21(13)4-10-11(12(15)16)18-6-20(9)10/h1-3,5-6,12H,4H2 Key:AFJRYPJIKHMNGL-UHFFFAOYSA-N

Ro4938581 is a nootropic drug invented in 2009 by a team working for Hoffmann-La Roche, which acts as a subtype-selective inverse agonist at the α₅ subtype of the benzodiazepine binding site on the GABA_A receptor. It has good selectivity for the α₅ subtype and did not produce convulsant or anxiogenic effects in animal studies, making it a promising potential nootropic.^[1][2][3] Ro4938581 and a related derivative basmisanil (RG-1662, RO5186582) have subsequently been investigated for the alleviation of cognitive dysfunction in Down syndrome.^[4][5]

See also

• α₅IA
• L-655,708
• PWZ-029
• TB-21007

References

1. Ballard, T. M.; Knoflach, F. D. R.; Prinssen, E.; Borroni, E.; Vivian, J. A.; Basile, J.; Gasser, R.; Moreau, J. L.; Wettstein, J. G.; Buettelmann, B.; Knust, H.; Thomas, A. W.; Trube, G.; Hernandez, M. C. (2008). "RO4938581, a novel cognitive enhancer acting at GABAA α5 subunit-containing receptors". Psychopharmacology. 202 (1–3): 207–223. doi:10.1007/s00213-008-1357-7. PMID 18936916.
2. Knust, H.; Achermann, G.; Ballard, T.; Buettelmann, B.; Gasser, R.; Fischer, H.; Hernandez, M. C.; Knoflach, F. D. R.; Koblet, A.; Stadler, H.; Thomas, A. W.; Trube, G.; Waldmeier, P. (2009). "The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA α5 inverse agonists for the treatment of cognitive dysfunction". Bioorganic & Medicinal Chemistry Letters. 19 (20): 5940–5944. doi:10.1016/j.bmcl.2009.08.053. PMID 19762240.
3. Redrobe, J. P.; Elster, L.; Frederiksen, K.; Bundgaard, C.; De Jong, I. E. M.; Smith, G. P.; Bruun, A. T.; Larsen, P. H.; Didriksen, M. (2011). "Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats". Psychopharmacology. 221 (3): 451–468. doi:10.1007/s00213-011-2593-9. PMID 22124672.
4. Martinez-Cue, C.; Martínez, P.; Rueda, N.; Vidal, R.; García, S.; Vidal, V.; Corrales, A.; Montero, J. A.; Pazos, A.; Flórez, J.; Gasser, R.; Thomas, A. W.; Honer, M.; Knoflach, F.; Trejo, J. L.; Wettstein, J. G.; Hernández, M. -C. (2013). "Reducing GABAA 5 Receptor-Mediated Inhibition Rescues Functional and Neuromorphological Deficits in a Mouse Model of Down Syndrome". Journal of Neuroscience. 33 (9): 3953–3966. doi:10.1523/JNEUROSCI.1203-12.2013. PMID 23447605.
5. Inhibiting Inhibition to Treat Down Syndrome Symptoms