2C-B-F-hemiFLY-α6 was first described in thescientific literature by 1995.[4][3] The compound resulted in conclusions thatphenethylamines andlysergamides do not necessarily interact with the serotonin 5-HT2A receptor in the same manner.[1][2] Following the negative findings, further investigation in this area was discontinued.[2]
Ananalogue of 2C-B-5-hemiFLY-α6 with theamine modified showed not only high-affinity partial agonism at the serotonin 5-HT2A receptor but also partially substituted for LSD andDOI in rodent drug discrimination tests.[2][5]
^abcdefghiBlaazer AR, Smid P, Kruse CG (September 2008)."Structure-activity relationships of phenylalkylamines as agonist ligands for 5-HT(2A) receptors".ChemMedChem.3 (9):1299–1309.doi:10.1002/cmdc.200800133.PMID18666267.Substituted tetrahydronaphthofurans have recently been synthesized as phenylalkylamine–ergoline composite molecules designed to mimic the A, B and C ring structure of ergolines.[198] Pharmacological evaluation of compound 42 revealed binding affinities at [125I]DOI-labeled cloned human 5-HT2A (Ki= 13.0 nm), and 5-HT2C (Ki=5.96 nm) receptors, which is 20–30-fold less than the affinity of 39 for these sites. Moreover, these compounds lacked LSD-like behavioral effects in a DD model. Based on these results, further work on structural similarities between ergolines and phenylalkylamines has ceased.[198, 199] ] Investigation into the 2-aminoalkyl side chain orientation led to the synthesis of analogue 43, with a nonplanar side chain. The affinity of compound 43 (Ki=2.6 nm), for [125I]DOI-labeled cloned rat 5-HT2A receptors, was close that of DOB (16, Ki= 2.2 nm) and LSD (3, Ki=3.5 nm). In a functional assay measuring IP3 accumulation, compound 43 was shown to be a partial agonist (EC50=120 nm; 33% of 5-HT stimulation), and it displayed partial substitution in LSD and DOI-trained rats.[199] One conclusion is that the side chain of ligand 43 might not possess the optimal dihedral angle for full receptor activation.
^abcdefMonte AP, Marona-Lewicka D, Lewis MM, Mailman RB, Wainscott DB, Nelson DL, et al. (June 1998). "Substituted naphthofurans as hallucinogenic phenethylamine-ergoline hybrid molecules with unexpected muscarinic antagonist activity".Journal of Medicinal Chemistry.41 (12):2134–2145.doi:10.1021/jm980076u.PMID9622555.
^abcdChambers JJ, Parrish JC, Jensen NH, Kurrasch-Orbaugh DM, Marona-Lewicka D, Nichols DE (July 2003). "Synthesis and pharmacological characterization of a series of geometrically constrained 5-HT(2A/2C) receptor ligands".Journal of Medicinal Chemistry.46 (16):3526–3535.doi:10.1021/jm030064v.PMID12877591.
