Langbahn Team – Weltmeisterschaft

MRK-409

MRK-409[1]
Names
IUPAC name
7-Cyclobutyl-3-(2,6-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine
Other names
  • MK-0343
  • 1,2,4-Triazolo(4,3-b)pyridazine, 7-cyclobutyl-3-(2,6-difluorophenyl)-6-((1-methyl-1H-1,2,4-triazol-5-yl)methoxy)-
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
DrugBank
UNII
  • InChI=1S/C19H17F2N7O/c1-27-16(22-10-23-27)9-29-19-12(11-4-2-5-11)8-15-24-25-18(28(15)26-19)17-13(20)6-3-7-14(17)21/h3,6-8,10-11H,2,4-5,9H2,1H3
    Key: GOIFCXRIFSYPFG-UHFFFAOYSA-N
  • CN1C(=NC=N1)COC2=NN3C(=NN=C3C4=C(C=CC=C4F)F)C=C2C5CCC5
Properties
C19H17F2N7O
Molar mass 397.390 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

MRK-409, also known as MK-0343, is a GABAA receptor partial agonist.[2]

It was designed to be a non-sedative anxiolytic, however its development was halted because it produced sedation in humans.[3]

Pharmacodynamics

Despite lacking the benzodiazepine chemical structure, MRK-409 acts on the benzodiazepine binding site, it is therefore a nonbenzodiazepine.

MRK-409 binds to the α1, α2, α3 and α5 subunits of the GABAA receptor.[4]

In rats, it produces minimal to no sedation, however it produces sedation in humans at doses above 1 mg.[3][5]

References

  1. ^ "1,2,4-Triazolo(4,3-b)pyridazine, 7-cyclobutyl-3-(2,6-difluorophenyl)-6-((1-methyl-1H-1,2,4-triazol-5-yl)methoxy)-".
  2. ^ "MRK-409". go.drugbank.com. Retrieved 2024-02-09.
  3. ^ a b Atack, John R. (2010). "GABAA receptor alpha2/alpha3 subtype-selective modulators as potential nonsedating anxiolytics". Current Topics in Behavioral Neurosciences. 2: 331–360. doi:10.1007/7854_2009_30. ISBN 978-3-642-02911-0. ISSN 1866-3370. PMID 21309116.
  4. ^ Atack, J. R.; Wafford, K. A.; Street, L. J.; Dawson, G. R.; Tye, S.; Van Laere, K.; Bormans, G.; Sanabria-Bohórquez, S. M.; De Lepeleire, I.; de Hoon, J. N.; Van Hecken, A.; Burns, H. D.; McKernan, R. M.; Murphy, M. G.; Hargreaves, R. J. (2011). "MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans". Journal of Psychopharmacology. 25 (3): 314–328. doi:10.1177/0269881109354927. ISSN 1461-7285. PMID 20147571. S2CID 5181868.
  5. ^ Atack, J. R.; Hallett, D. J.; Tye, S.; Wafford, K. A.; Ryan, C.; Sanabria-Bohórquez, S. M.; Eng, Wai-Si; Gibson, R. E.; Burns, H. D.; Dawson, G. R.; Carling, R. W.; Street, L. J.; Pike, A.; De Lepeleire, I.; Van Laere, K. (2011). "Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist". Journal of Psychopharmacology. 25 (3): 329–344. doi:10.1177/0269881109354928. ISSN 1461-7285. PMID 20156926. S2CID 37703616.
Quelle: https://en.wikipedia.org/wiki/MRK-409_(MK-0343)