2C-B-5-hemiFLY-α6

Pharmaceutical compound From Wikipedia, the free encyclopedia

2C-B-5-hemiFLY-α6, also known as BNAP, is a serotonin receptor modulator of the phenethylamine and FLY families related to the psychedelic drugs 2C-B and DOB.^[1]^[2]^[3] It is a cyclized phenethylamine with a partial ergoline like chemical structure.^[1]^[2]^[3] Its tricyclic structure mimics the A, B, and C rings of LSD.^[2]^[1]

Other namesBNAP

Drug classSerotonin receptor modulator

ATC code

None

ChemSpider

21376194

Quick facts Clinical data, Other names ...

2C-B-5-hemiFLY-α6
Clinical data

Other names	BNAP
Drug class	Serotonin receptor modulator
ATC code	None
Identifiers
IUPAC name 8-bromo-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan-4-amine
ChemSpider	21376194
Chemical and physical data
Formula	C₁₂H₁₄BrNO₂
Molar mass	284.153 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES COc1cc(Br)c2c3c1CC(N)CC3CO2
InChI InChI=1S/C12H14BrNO2/c1-15-10-4-9(13)12-11-6(5-16-12)2-7(14)3-8(10)11/h4,6-7H,2-3,5,14H2,1H3 Key:CLZKGXPLDDUCQZ-UHFFFAOYSA-N

Pharmacology

The more active syn stereoisomer of the drug shows high affinity for the human serotonin 5-HT_2A and 5-HT_2C receptors with agonist radioligands (K_i = 13–16 nM and 4–6 nM, respectively).^[2]^[1]^[4]^[5] These affinities were 20- to 30-fold lower than those of the related drug DOB-FLY.^[2]^[4] The stereoisomer also showed much weaker affinity for the serotonin 5-HT_2B receptor with agonist radioligand (K_i = 280 nM) and for the serotonin 5-HT_1A receptor (K_i = 960 nM).^[4]^[5] Affinities for rat serotonin receptors and for human serotonin receptors with antagonist radioligands were much lower.^[3] A subsequent study showed the more active enantiomer to be a partial agonist of the rat serotonin 5-HT_2A receptor (EC₅₀Tooltip half-maximal effective concentration = 2,090 nM; E_maxTooltip maximal efficacy = 63%).^[6]^[5] Neither stereoisomer produced LSD-like effects in rodent drug discrimination tests.^[2]^[1]^[3] Unexpectedly, the more active stereoisomer showed relatively high affinity for the five muscarinic acetylcholine receptors (K_i = 12–81 nM).^[1]^[4]^[3]

History

2C-B-F-hemiFLY-α6 was first described in the scientific literature by 1995.^[4]^[3] The compound resulted in conclusions that phenethylamines and lysergamides do not necessarily interact with the serotonin 5-HT_2A receptor in the same manner.^[1]^[2] Following the negative findings, further investigation in this area was discontinued.^[2]

Analogues

An analogue of 2C-B-5-hemiFLY-α6 with the amine modified showed not only high-affinity partial agonism at the serotonin 5-HT_2A receptor but also partially substituted for LSD and DOI in rodent drug discrimination tests.^[2]^[5]

References

[1]
Trachsel D, Lehmann D, Enzensperger C (2013). Phenethylamine: von der Struktur zur Funktion [Phenethylamines: From Structure to Function]. Nachtschatten-Science (in German) (1 ed.). Solothurn: Nachtschatten-Verlag. p. 847. ISBN 978-3-03788-700-4. OCLC 858805226.
[2]
Blaazer 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. PMID 18666267. 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.
[3]
Monte 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. PMID 9622555.
[4]
Monte AP (August 1995). Structure-activity relationships of hallucinogens: Design, synthesis, and pharmacological evaluation of a series of conformationally restricted phenethylamines (Ph.D. thesis). Purdue University.
[5]
Chambers 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. PMID 12877591.
[6]
Chambers JJ (2002). Use of conformationally-restricted analogues and homology modeling to provide insight into the nature of the 5-HT2A receptor agonist binding site (Thesis). Purdue University. Table 2. Results of radioligand competition binding studies at cloned receptors. [...] Table 3. Results of the IP3 accumulation studies at cloned rat 5-HT2A receptors. [...]

2C-B-5-hemiFLY-α6

Pharmacology

History

Analogues

See also

References

External links

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