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HIOC
Clinical data
ATC code
  • None
Identifiers
  • N-[2-(5-Hydroxy-1H-indol-3-yl)ethyl]-2-oxo-3-piperidinecarboxamide
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC16H19N3O3
Molar mass301.346 g·mol−1
3D model ( JSmol)
  • c1cc2c(cc1O)c(c[nH]2)CCNC(=O)C3CCCNC3=O
  • InChI=1S/C16H19N3O3/c20-11-3-4-14-13(8-11)10(9-19-14)5-7-18-16(22)12-2-1-6-17-15(12)21/h3-4,8-9,12,19-20H,1-2,5-7H2,(H,17,21)(H,18,22)
  • Key:ZIMKJLALTRLXJO-UHFFFAOYSA-N

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 was published in 2015. [5]

See also

References

  1. ^ Longo FM, Massa SM (July 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. PMID  23977697. S2CID  33597483.
  2. ^ a b c d e Iuvone PM, Boatright JH, Tosini G, Ye K (2014). "N-Acetylserotonin: Circadian Activation of the BDNF Receptor and Neuroprotection in the Retina and Brain". Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology. Vol. 801. pp. 765–771. doi: 10.1007/978-1-4614-3209-8_96. ISBN  978-1-4614-3208-1. PMC  4069859. PMID  24664769.
  3. ^ a b c d Shen J, Ghai K, Sompol P, Liu X, Cao X, Iuvone PM, Ye K (February 2012). "N-acetyl serotonin derivatives as potent neuroprotectants for retinas". Proceedings of the National Academy of Sciences of the United States of America. 109 (9): 3540–3545. Bibcode: 2012PNAS..109.3540S. doi: 10.1073/pnas.1119201109. PMC  3295250. PMID  22331903.
  4. ^ Tosini G, Ye K, Iuvone PM (December 2012). "N-acetylserotonin: neuroprotection, neurogenesis, and the sleepy brain". The Neuroscientist. 18 (6): 645–653. doi: 10.1177/1073858412446634. PMC  3422380. PMID  22585341.
  5. ^ Setterholm NA, McDonald FE, Boatright JH, Iuvone PM (June 2015). "Gram-scale, chemoselective synthesis of N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC)". Tetrahedron Letters. 56 (23): 3413–3415. doi: 10.1016/j.tetlet.2015.01.167. PMC  4445863. PMID  26028783.


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