QH-II-66

QH-II-66

Identifiers
IUPAC name 7-ethynyl-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one
CAS Number	183239-39-6
PubChem (CID)	9838431
ChemSpider	8014151
ChEMBL	CHEMBL174535
Chemical and physical data
Formula	C18H14N2O
Molar mass	274.33
3D model (Jmol)	Interactive image
SMILES O=C1N(C)C2=C(C(C3=CC=CC=C3)=NC1)C=C(C=C2)C#C
InChI InChI=1S/C18H14N2O/c1-3-13-9-10-16-15(11-13)18(14-7-5-4-6-8-14)19-12-17(21)20(16)2/h1,4-11H,12H2,2H3 Key:FESCSZDQOFYRDR-UHFFFAOYSA-N
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QH-II-66^[1] (QH-ii-066) is a sedative drug which is a benzodiazepine derivative.^[2] It produces some of the same effects as other benzodiazepines, but is much more selective than most other drugs of this class and so produces somewhat less sedation and ataxia than other related drugs such as diazepam and triazolam, although it still retains anticonvulsant effects.^[3]

QH-ii-066 is a highly subtype-selective GABA_A agonist which was designed to bind selectively to the α₅ subtype of GABA_A receptors.^[4]

The α₅ subtype (and to a lesser extent the α₁ subtype) of GABA_A are two of the most important targets in the brain that produce the effects of alcohol,^[5] and so one of the purposes for which QH-ii-066 was developed was to reproduce the GABAergic effects of alcohol separately from its other actions.^[6]

QH-ii-066 replicates some of the effects of alcohol, such as sedation and ataxia, but does not increase appetite, as this effect seems to be produced by the α₁ subtype of GABA_A rather than α₅.^[7] The inverse agonist Ro15-4513, which blocks the α₄ subtype of GABA_A, reverses the effects of alcohol, suggesting that this subtype is also important in producing the subjective effects of alcohol intoxication.^[8]

See also

• SH-053-R-CH3-2′F

References

1. US Patent Application 2006/3995 A1 Stereospecific anxiolytic and anticonvulsant agents with reduced muscle-relaxant, sedative-hypnotic and ataxic effects
2. Huang Q, He X, Ma C, Liu R, Yu S, Dayer CA, Wenger GR, McKernan R, Cook JM (2000). "Pharmacophore/receptor models for GABA_A/BzR subtypes (α₁β₃γ₂, α₅β₃γ₂, and α₆β₃γ₂) via a comprehensive ligand-mapping approach". J. Med. Chem. 43 (1): 71–95. doi:10.1021/jm990341r. PMID 10633039.
3. James M. Cook, Qi Huang, Xiaohui He, Xioayan Li, Jianming Yu, Dongmei Han, Snjezana Lelas, John F. McElroy. US71191961
4. Huang Q, Zhang W, Liu R, McKernan RM, Cook JM (1996). "Benzo-fused benzodiazepines employed as topological probes for the study of benzodiazepine receptor subtypes". Medicinal Chemistry Research. 6 (3): 384–391.
5. Platt DM, Duggan A, Spealman RD, Cook JM, Li X, Yin W, Rowlett JK (2005). "Contribution of α₁ GABA_A and α₅ GABA_A receptor subtypes to the discriminative stimulus effects of ethanol in squirrel monkeys". J. Pharmacol. Exp. Ther. 313 (2): 658–67. doi:10.1124/jpet.104.080275. PMID 15650112.
6. Hodge CW, Grant KA, Becker HC, Besheer J, Crissman AM, Platt DM, Shannon EE, Shelton KL (2006). "Understanding how the brain perceives alcohol: neurobiological basis of ethanol discrimination". Alcohol. Clin. Exp. Res. 30 (2): 203–13. doi:10.1111/j.1530-0277.2006.00024.x. PMID 16441269.
7. Duke AN, Platt DM, Cook JM, Huang S, Yin W, Mattingly BA, Rowlett JK (2006). "Enhanced sucrose pellet consumption induced by benzodiazepine-type drugs in squirrel monkeys: role of GABA_A receptor subtypes". Psychopharmacology (Berl.). 187 (3): 321–30. doi:10.1007/s00213-006-0431-2. PMID 16783540.
8. Wallner M, Hanchar HJ, Olsen RW (2006). "Low-dose alcohol actions on α4β3δ GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513". Proc. Natl. Acad. Sci. U.S.A. 103 (22): 8540–5. doi:10.1073/pnas.0600194103. PMC 1482527. PMID 16698930.