TFMBOX

TFMBOX
Clinical data
Other names	"Compound 5c"
Drug class	Serotonin receptor modulator; Serotonergic psychedelic; Hallucinogen
Identifiers
	IUPAC name 7-methoxy-8-(trifluoromethyl)-2,3,4,5-tetrahydro-1-benzoxepin-4-amine;
CAS Number	774160-02-0 ; 173989-93-0 (HCl);
Chemical and physical data
Formula	C12H14F3NO2
Molar mass	261.244 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COc1cc2CC(N)CCOc2cc1C(F)(F)F;
	InChI InChI=1S/C12H14F3NO2/c1-17-11-5-7-4-8(16)2-3-18-10(7)6-9(11)12(13,14)15/h5-6,8H,2-4,16H2,1H3; Key:NAOXZRLWFAOHAP-UHFFFAOYSA-N;

TFMBOX is a putative serotonergic psychedelic of the phenethylamine and benzoxepin ("BOX") families.^[1]^[2]^[3] It is the cyclized phenethylamine analogue of DOTFM and 2C-TFM in which the α carbon has been connected to the 2-methoxy group via an ethyl chain to form a benzoxepin ring system.^[1]^[2]

Interactions

Pharmacology

Pharmacodynamics

The drug was assessed at and showed affinity for the serotonin 5-HT_2A and 5-HT_1A receptors, with K_i values of 340 nM and 1,300 nM, respectively.^[2] Its affinity for the serotonin 5-HT_2A receptor was about 15-fold lower than that of DOB and DOI, whereas its affinity for the serotonin 5-HT_1A receptor was the same as that of DOI and was about half that of DOB.^[2] TFMBOX also very weakly inhibited the reuptake of serotonin (IC₅₀Tooltip half-maximal inhibitory concentration = 9,900 nM), but did not affect dopamine or norepinephrine reuptake (IC₅₀ = >50,000–100,000 nM).^[2] The drug fully substituted for LSD in rodent drug discrimination tests, albeit with about one-third of the potency of DOB and 2C-B.^[2]

Chemistry

Analogues

Other "BOX" drugs that have been assessed include BOX (the cyclized analogue of 2C-H and DOH), BBOX (the cyclized analogue of 2C-B and DOB), and IBOX (the cyclized analogue of 2C-I and DOI).^[2]^[3] However, BBOX and IBOX only partially substituted for LSD in drug discrimination tests.^[2]^[3]^[4]

Chemical structures of BOX compounds

BOX
TFMBOX
BBOX
IBOX

History

TFMBOX was first described in the scientific literature by Nicholas Cozzi, a student of David E. Nichols, by 1994.^[2]^[3]

References

1 2 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. pp. 852–853. ISBN 978-3-03788-700-4. OCLC 858805226. Retrieved 31 January 2025.
1 2 3 4 5 6 7 8 9 Monte AP, Marona-Lewicka D, Cozzi NV, Nelson DL, Nichols DE (1995). "Conformationally Restricted Tetrahydro-1-Benzoxepin Analogs of Hallucinogenic Phenethylamines". Medicinal Chemistry Research. 5 (651–663).
1 2 3 4 Cozzi NV (1994). Pharmacological studies of some psychoactive phenylalkylamines: Entactogens, hallucinogens, and anorectics (Ph.D. thesis). University of Wisconsin, Madison. Retrieved 15 April 2025.
↑ 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. Retrieved 15 April 2025.

External links

[Trachsel2013-1] 1 2 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. pp. 852–853. ISBN 978-3-03788-700-4. OCLC 858805226. Retrieved 31 January 2025.

[MonteMarona-LewickaCozzi1995-2] 1 2 3 4 5 6 7 8 9 Monte AP, Marona-Lewicka D, Cozzi NV, Nelson DL, Nichols DE (1995). "Conformationally Restricted Tetrahydro-1-Benzoxepin Analogs of Hallucinogenic Phenethylamines". Medicinal Chemistry Research. 5 (651–663).

[Cozzi1994-3] 1 2 3 4 Cozzi NV (1994). Pharmacological studies of some psychoactive phenylalkylamines: Entactogens, hallucinogens, and anorectics (Ph.D. thesis). University of Wisconsin, Madison. Retrieved 15 April 2025.

[Monte1995-4] 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. Retrieved 15 April 2025.

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