GL-II-73

GL-II-73 (GL-ii-073) is a benzodiazepine derivative related in chemical structure to compounds such as midazolam and adinazolam. It is described as an α₅ preferring positive allosteric modulator of the benzodiazepine site of GABA_A receptors, with weaker activity at α₂ and α₃ and no significant affinity for the α₁ subtype. In animal tests it was found to produce effects consistent with antidepressant, anxiolytic and nootropic actions.^{[1][2][3][4][5][6][7]}

GL-II-73

Identifiers
IUPAC name (4R)-8-ethynyl-6-(2-fluorophenyl)-N,N,4-trimethyl-4H-benzo[f]imidazo[1,5-a] [1,4]diazepine-3-carboxamide
PubChem CID	130439778
Chemical and physical data
Formula	C23H19FN4O
Molar mass	386.430 g·mol−1
3D model (JSmol)	Interactive image
SMILES CN(C)C(=O)c4ncn2c4[C@@H](C)N=C(c1cc(C#C)ccc12)c3ccccc3F
InChI InChI=1S/C23H19FN4O/c1-5-15-10-11-19-17(12-15)20(16-8-6-7-9-18(16)24)26-14(2)22-21(23(29)27(3)4)25-13-28(19)22/h1,6-14H,2-4H3/t14-/m1/s1 Key:LNPOWXXHIUMIKI-CQSZACIVSA-N

See also

• Imidazenil
• Pyeazolam
• QH-II-66
• SH-I-048A
• SH-053-R-CH3-2'F
• Ro4938581

References

1. CA 3016491, Cook JM, Li G, Poe M, Savic M, Sibille E, "Treatment of cognitive and mood symptoms in neurodegenerative and neuropsychiatric disorders with alpha5-containing gabaa receptor agonists.", published 21 September 2017, assigned to Centre for Addiction and Mental Health, Faculty Of Pharmacy, University of Belgrade and UWM Res Foundation Inc
2. Prevot TD, Li G, Vidojevic A, Misquitta KA, Fee C, Santrac A, Knutson DE, Stephen MR, Kodali R, Zahn NM, Arnold LA (January 2018). "Potential combined pro-cognitive, anxiolytic and antidepressant properties of novel GABAA receptor positive modulators with preferential efficacy at the α5-subunit" (PDF). bioRxiv: 332908. doi:10.1101/332908. S2CID 90987308.
3. Prevot TD, Li G, Vidojevic A, Misquitta KA, Fee C, Santrac A, Knutson DE, Stephen MR, Kodali R, Zahn NM, Arnold LA, Scholze P, Fisher JL, Marković BD, Banasr M, Cook JM, Savic M, Sibille E (April 2019). "Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles". Molecular Neuropsychiatry. 5 (2): 84–97. doi:10.1159/000496086. PMC 6528097. PMID 31192221.
4. Sibille E (February 2019). "Brain Inhibitory GABAergic Function and Cognitive Deficits: Mechanisms and Therapeutic Targeting" (PDF). Presentation for AAAS. Archived from the original (PDF) on 2019-04-12. Retrieved 2019-03-09.
5. Maramai S, Benchekroun M, Ward SE, Atack JR (April 2020). "Subtype Selective γ-Aminobutyric Acid Type A Receptor (GABA_AR) Modulators Acting at the Benzodiazepine Binding Site: An Update". Journal of Medicinal Chemistry. 63 (7): 3425–3446. doi:10.1021/acs.jmedchem.9b01312. PMID 31738537. S2CID 208171129.
6. Bernardo A, Lee P, Marcotte M, Mian MY, Rezvanian S, Sharmin D, Kovačević A, Savić MM, Cook JM, Sibille E, Prevot TD (August 2022). "Symptomatic and neurotrophic effects of GABAA receptor positive allosteric modulation in a mouse model of chronic stress". Neuropsychopharmacology. 47 (9): 1608–1619. doi:10.1038/s41386-022-01360-y. PMC 9283409. PMID 35701547.
7. Perez SM, McCoy AM, Prevot TD, Mian MY, Carreno FR, Frazer A, Cook JM, Sibille E, Lodge DJ (January 2023). "Hippocampal α5-GABA_A Receptors Modulate Dopamine Neuron Activity in the Rat Ventral Tegmental Area". Biological Psychiatry Global Open Science. 3 (1): 78–86. doi:10.1016/j.bpsgos.2021.12.010. PMC 9874136. PMID 36712569.