Indazolethylamine

Indazolethylamines, or indazolylethylamines, are a group of indazole derivatives closely related to the tryptamines (indolylethylamines). Examples include the simple indazolethylamines AL-34662 and O-methyl-AL-34662 and the cyclized indazolethylamines AL-38022A, VU6067416, and YM-348. These indazolethylamines are known to act as serotonin 5-HT₂ receptor agonists. Some of them, such as O-methyl-AL-34662 and AL-38022A, have been shown to produce psychedelic-like effects in animals similarly to tryptamines. ^{[1] [2] [3] [4] [5] [6] [7] [8]}

Chemical structures of selected indazolethylamines

• 
  AL-34662
• 
  O-Methyl-AL-34662
• 
  AL-38022A
• 
  YM-348
• 
  VU6067416

See also

• Substituted tryptamine
• Cyclized tryptamine
• Indolizinylethylamine
• Tetrahydropyridinylpyrrolopyridine

References

1. Nichols, David E. (2012). "Structure–activity relationships of serotonin 5‐HT 2A agonists" (PDF). Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi: 10.1002/wmts.42 . ISSN   2190-460X.
2. Nichols DE (2018). "Chemistry and Structure-Activity Relationships of Psychedelics". Curr Top Behav Neurosci. 36: 1–43. doi:10.1007/7854_2017_475. PMID   28401524.
3. Kargbo RB (November 2023). "Small-Molecule Heterocyclic Compounds: Gq-Biased Agonists for the 5-HT2A Receptor in Neuropsychiatric Treatment". ACS Medicinal Chemistry Letters. 14 (11): 1498–1500. doi: 10.1021/acsmedchemlett.3c00444 . PMC   10641896 . PMID   37974947.
4. May JA, Dantanarayana AP, Zinke PW, McLaughlin MA, Sharif NA (January 2006). "1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity". Journal of Medicinal Chemistry. 49 (1): 318–328. doi:10.1021/jm050663x. PMID   16392816.
5. Shimada I, Maeno K, Kazuta K, Kubota H, Kimizuka T, Kimura Y, Hatanaka K, Naitou Y, Wanibuchi F, Sakamoto S, Tsukamoto S (February 2008). "Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists". Bioorganic & Medicinal Chemistry. 16 (4): 1966–1982. doi:10.1016/j.bmc.2007.10.100. PMID   18035544.
6. May JA, Sharif NA, Chen HH, Liao JC, Kelly CR, Glennon RA, Young R, Li JX, Rice KC, France CP (January 2009). "Pharmacological properties and discriminative stimulus effects of a novel and selective 5-HT2 receptor agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine]". Pharmacol Biochem Behav. 91 (3): 307–314. doi:10.1016/j.pbb.2008.07.015. PMC   3763814 . PMID   18718483.
7. May JA, Sharif NA, McLaughlin MA, Chen HH, Severns BS, Kelly CR, Holt WF, Young R, Glennon RA, Hellberg MR, Dean TR (November 2015). "Ocular Hypotensive Response in Nonhuman Primates of (8R)-1-[(2S)-2-Aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol a Selective 5-HT2 Receptor Agonist". J Med Chem. 58 (22): 8818–8833. doi:10.1021/acs.jmedchem.5b00857. PMID   26551970.
8. Kimura Y, Hatanaka K, Naitou Y, Maeno K, Shimada I, Koakutsu A, Wanibuchi F, Yamaguchi T (January 2004). "Pharmacological profile of YM348, a novel, potent and orally active 5-HT2C receptor agonist". Eur J Pharmacol. 483 (1): 37–43. doi:10.1016/j.ejphar.2003.10.004. PMID   14709324.