HIOC explained
| Iupac Name: | N-[2-(5-Hydroxy-1''H''-indol-3-yl)ethyl]-2-oxo-3-piperidinecarboxamide |
| Width: | 225px |
| Cas Number: | 314054-36-9 |
| Atc Prefix: | None |
| Pubchem: | 5012758 |
| Unii: | JC3KZQ72GW |
| Chemspiderid: | 4192105 |
| C: | 16 |
| H: | 19 |
| N: | 3 |
| O: | 3 |
| Smiles: | c1cc2c(cc1O)c(c[nH]2)CCNC(=O)C3CCCNC3=O |
| Stdinchi: | 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) |
| Stdinchikey: | 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).[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). It is described as producing long-lasting activation of the TrkB receptor and downstream signaling kinases associated with the receptor. HIOC is systemically active and is able to penetrate the blood-brain-barrier. In animal studies, HIOC was found to robustly protect against glutamate-induced excitotoxicity, an action which was TrkB-dependent.
A chemical synthesis of HIOC was published in 2015.[5]
See also
- Tropomyosin receptor kinase B § Agonists
Notes and References
- Longo FM, Massa SM . Small-molecule modulation of neurotrophin receptors: a strategy for the treatment of neurological disease . Nature Reviews. Drug Discovery . 12 . 7 . 507–525 . July 2013 . 23977697 . 10.1038/nrd4024 . 33597483 .
- Book: Iuvone PM, Boatright JH, Tosini G, Ye K . Retinal Degenerative Diseases . N-Acetylserotonin: Circadian Activation of the BDNF Receptor and Neuroprotection in the Retina and Brain . Advances in Experimental Medicine and Biology . 801 . 765–771 . 2014 . 24664769 . 4069859 . 10.1007/978-1-4614-3209-8_96 . 978-1-4614-3208-1 .
- Shen J, Ghai K, Sompol P, Liu X, Cao X, Iuvone PM, Ye K . 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 . February 2012 . 22331903 . 3295250 . 10.1073/pnas.1119201109 . free . 2012PNAS..109.3540S .
- Tosini G, Ye K, Iuvone PM . N-acetylserotonin: neuroprotection, neurogenesis, and the sleepy brain . The Neuroscientist . 18 . 6 . 645–653 . December 2012 . 22585341 . 3422380 . 10.1177/1073858412446634 .
- Setterholm NA, McDonald FE, Boatright JH, Iuvone PM . 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 . June 2015 . 26028783 . 4445863 . 10.1016/j.tetlet.2015.01.167 .
