HIOC

HIOC
Systematic (IUPAC) name
N-[2-(5-Hydroxy-1H-indol-3-yl)ethyl]-2-oxo-3-piperidinecarboxamide
Identifiers
ATC code None
PubChem CID 5012758
ChemSpider 4192105
Chemical data
Formula C16H19N3O3
Molar mass 301.340

HIOC is a small-molecule agent which acts as a selective TrkB receptor agonist (active at at least 100 nM; prominent activation at 500 nM).[1][2][3] It was derived from N-acetylserotonin (NAS).[2][3][4] Relative to NAS, HIOC possesses greater potency and a longer half-life (~30 min or less for NAS in rats, while HIOC is still detectable up to 24 hours after administration to mice; ~4 hour half-life for HIOC in mouse brain tissues).[2][3] It is described as producing long-lasting activation of the TrkB receptor and downstream signaling kinases associated with the receptor.[2] HIOC is systemically-active and is able to penetrate the blood-brain-barrier.[2] In animal studies, HIOC was found to robustly protect against glutamate-induced excitotoxicity, an action which was TrkB-dependent.[3]

A chemical synthesis of HIOC has been published recently.[5]

See also

References

  1. ↑ Longo, Frank M.; Massa, Stephen M. (2013). "Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease". Nature Reviews Drug Discovery 12 (7): 507–525. doi:10.1038/nrd4024. ISSN 1474-1776.
  2. 1 2 3 4 5 Iuvone, P. Michael; Boatright, Jeffrey H.; Tosini, Gianluca; Ye, Keqiang (2014). "N-Acetylserotonin: Circadian Activation of the BDNF Receptor and Neuroprotection in the Retina and Brain" 801: 765–771. doi:10.1007/978-1-4614-3209-8_96. ISSN 0065-2598.
  3. 1 2 3 4 Shen, J.; Ghai, K.; Sompol, P.; Liu, X.; Cao, X.; Iuvone, P. M.; Ye, K. (2012). "N-acetyl serotonin derivatives as potent neuroprotectants for retinas". Proceedings of the National Academy of Sciences 109 (9): 3540–3545. doi:10.1073/pnas.1119201109. ISSN 0027-8424.
  4. ↑ Tosini, G.; Ye, K.; Iuvone, P. M. (2012). "N-Acetylserotonin: Neuroprotection, Neurogenesis, and the Sleepy Brain". The Neuroscientist 18 (6): 645–653. doi:10.1177/1073858412446634. ISSN 1073-8584.
  5. ↑ Setterholm NA, McDonald FE, Boatright JH, Iuvone PM (2015). "Gram-scale, chemoselective synthesis of N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC)". Tetrahedron Lett. 56 (23): 3413–3415. doi:10.1016/j.tetlet.2015.01.167. PMID 26028783.



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