SH-053-R-CH3-2′F

SH-053-R-CH3-2′F is a drug used in scientific research which is a benzodiazepine derivative. It produces some of the same effects as other benzodiazepines, but is much more subtype-selective than most other drugs of this class, having high selectivity, binding affinity and efficacy at the α5 subtype of the GABAA receptor. This gives much tighter control of the effects produced, and so while SH-053-R-CH3-2′F retains sedative and anxiolytic effects, it does not cause ataxia at moderate doses.[1] SH-053-R-CH3-2′F also blocks the nootropic effects of the α5-selective inverse agonist PWZ-029, so amnesia is also a likely side effect.[2]

SH-053-R-CH3-2′F
Identifiers
IUPAC name
  • (R)-8-ethynyl-6-(2-fluorophenyl)-4-methyl-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic acid ethyl ester
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC23H18FN3O2
Molar mass387.414 g·mol−1
3D model (JSmol)
SMILES
  • Fc2ccccc2C1=NC(C)c3c(C(=O)OCC)ncn3-c(cc4)c1cc4C#C
InChI
  • InChI=1S/C23H18FN3O2/c1-4-15-10-11-19-17(12-15)20(16-8-6-7-9-18(16)24)26-14(3)22-21(23(28)29-5-2)25-13-27(19)22/h1,6-14H,5H2,2-3H3/t14-/m1/s1
  • Key:NGYKELBMVXBFSM-CQSZACIVSA-N

Replacement of the ester function by an amide, realized in analogs such as MP-III-022 and GL-II-73, improves selectivity, efficacy, and kinetic behavior.[3][4][5]

See also

References
  1. Savić MM, Huang S, Furtmüller R, Clayton T, Huck S, Obradović DI, et al. (January 2008). "Are GABAA receptors containing alpha5 subunits contributing to the sedative properties of benzodiazepine site agonists?". Neuropsychopharmacology. 33 (2): 332–339. doi:10.1038/sj.npp.1301403. PMID 17392731.
  2. Savić MM, Clayton T, Furtmüller R, Gavrilović I, Samardzić J, Savić S, et al. (May 2008). "PWZ-029, a compound with moderate inverse agonist functional selectivity at GABA(A) receptors containing alpha5 subunits, improves passive, but not active, avoidance learning in rats". Brain Research. 1208: 150–159. doi:10.1016/j.brainres.2008.02.020. PMC 2577822. PMID 18394590.
  3. Stamenić TT, Poe MM, Rehman S, Santrač A, Divović B, Scholze P, et al. (November 2016). "Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit". European Journal of Pharmacology. 791: 433–443. doi:10.1016/j.ejphar.2016.09.016. PMC 5107132. PMID 27639297.
  4. 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."
  5. Prevot TD, Li G, Vidojevic A, Misquitta KA, Fee C, Santrac A, et al. (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.
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