Besides 2C-Ph itself, a variety ofderivatives of 2C-Ph withsubstituents on the 4-position phenyl ring have beensynthesized and studied by Trachsel and colleagues.[1][2][3] These drugs, inclusive of 2C-Ph, have been denoted 2C-BI-1 to 2C-BI-12.[1][2][3]2C-BI-4 (the 2′-trifluoromethyl derivative),2C-BI-8 (the 4′-methoxy derivative), and2C-BI-12 (the 3′,4′-dimethoxy derivative) are agonists of the human serotonin 5-HT2A receptor with higher efficacy than 2C-Ph (EC50 = 37–2,408nM,Emax = 38–44%).[3] The effects of 2C-Ph and its derivatives in humans are unknown.[1][3] However, 2C-BI-8 and 2C-BI-12, the most potent agonists, in particular might have the potential forpsychedelic effects.[3]
2C-Ph was first described in thescientific literature, by Trachsel and Nichols and colleagues, in 2009.[1][2]
^abcdefTrachsel D, Nichols DE, Kidd S, Hadorn M, Baumberger F (May 2009). "4-aryl-substituted 2,5-dimethoxyphenethylamines: synthesis and serotonin 5-HT(2A) receptor affinities".Chemistry & Biodiversity.6 (5):692–704.doi:10.1002/cbdv.200800235.PMID19479848.
^abcdefghiLuethi D, Widmer R, Trachsel D, Hoener MC, Liechti ME (July 2019). "Monoamine receptor interaction profiles of 4-aryl-substituted 2,5-dimethoxyphenethylamines (2C-BI derivatives)".European Journal of Pharmacology.855:103–111.doi:10.1016/j.ejphar.2019.05.014.PMID31063768.
^abYempala T, Brea J, Loza MI, Matthies DJ, Zapata-Torres G, Cassels BK (February 2020)."Dibenzofuranylethylamines as 5-HT2A/2C Receptor Agonists".ACS Omega.5 (5):2260–2266.doi:10.1021/acsomega.9b03430.PMC7016908.PMID32064387.Regarding the weakly binding compound 3, which is practically devoid of (partial) agonist activity at both receptor subtypes, it may be seen as a cyclized version of the 5-HT2A antagonist 2-(2,5-dimethoxy-4-phenylphenyl)ethanamine (2C-phenyl, compound 7 in Trachsel et al., 2009).23 However, the orientation of the oxygen lone pairs on the dibenzofuran ring is "wrong" for hydrogen bonding,6,7 as corroborated by the higher affinities of 2C-phenyl and the "Fly" and "Dragonfly" compounds with "correct" orientations and pKi values of 6.11 and greater than 8, respectively, at the 5-HT2A receptor (the 5-HT2C affinities of 2C-phenyl and the "Fly/Dragonfly" compounds are not available, nor are their functional activities at this receptor). Nevertheless, it should be noted, however, that while 2C-H-Fly elicited a positive drug discrimination response in LSD-trained rats, suggesting that it is a 5-HT2A agonist, and 3 is a very weak partial agonist, 2C-phenyl is an antagonist at this receptor (Figure 6). [...] Figure 6. Comparison of the structures of compound 3, 2C-phenyl, and "Fly" (with dihydrofuran rings) and "Dragonfly" compounds (with furan rings).
Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as theList of trace amines,TAAR, andTAAR1 pages. See also:Receptor/signaling modulators
