From Wikipedia, the free encyclopedia
Abandoned drug
MRK-409
[1]
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Names
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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
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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)-
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Identifiers
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ChEMBL
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ChemSpider
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DrugBank
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UNII
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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
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CN1C(=NC=N1)COC2=NN3C(=NN=C3C4=C(C=CC=C4F)F)C=C2C5CCC5
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Properties
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C19H17F2N7O
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Molar mass
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397.390 g·mol−1
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Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
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Chemical compound
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
-
^
"1,2,4-Triazolo(4,3-b)pyridazine, 7-cyclobutyl-3-(2,6-difluorophenyl)-6-((1-methyl-1H-1,2,4-triazol-5-yl)methoxy)-".
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^
"MRK-409". go.drugbank.com. Retrieved 2024-02-09.
- ^
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.
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^ 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.
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^ 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.
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