4C-I

Other namesIodo-Ariadne; 4C-DOI; DOI-B; 4-Iodo-2,5-dimethoxy-α-ethylphenethylamine; 2,5-Dimethoxy-4-iodo-α-ethylphenethylamine

Routes of
administrationOral^[1]^[2]

Drug classSerotonin 5-HT₂ receptor agonist; Serotonin 5-HT_2A receptor agonist

ATC code

None

4C-I
Clinical data

Other names	Iodo-Ariadne; 4C-DOI; DOI-B; 4-Iodo-2,5-dimethoxy-α-ethylphenethylamine; 2,5-Dimethoxy-4-iodo-α-ethylphenethylamine
Routes of administration	Oral^[1]^[2]
Drug class	Serotonin 5-HT₂ receptor agonist; Serotonin 5-HT_2A receptor agonist
ATC code	None
Identifiers
IUPAC name 1-(4-iodo-2,5-dimethoxyphenyl)butan-2-amine
PubChem CID	44288588
ChemSpider	25047981
Chemical and physical data
Formula	C₁₂H₁₈INO₂
Molar mass	335.185 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CCC(CC1=CC(=C(C=C1OC)I)OC)N
InChI InChI=1S/C12H18INO2/c1-4-9(14)5-8-6-12(16-3)10(13)7-11(8)15-2/h6-7,9H,4-5,14H2,1-3H3 Key:KQTCNDCMXMIDEQ-UHFFFAOYSA-N

4C-I, also known as iodo-Ariadne, 4C-DOI, or DOI-B, as well as 4-iodo-2,5-dimethoxy-α-ethylphenethylamine, is a serotonin 5-HT₂ receptor agonist of the phenethylamine, phenylisobutylamine, and 4C families related to Ariadne (4C-D).^[1]^[2]^[3]^[4] It is a close analogue of the psychedelic drugs 2C-I and DOI, with 2C-I having no substitution at the α carbon, DOI having an α-methyl group, and 4C-I having an α-ethyl group.^[3]^[2] In his 1991 book PiHKAL (Phenethylamines I Have Known and Loved), Alexander Shulgin described testing 4C-I at doses of up to 4 mg orally, but observed no effects and did not assess higher doses.^[1]^[2] The drug is a potent agonist of the serotonin 5-HT_2A receptor.^[3] It shows similar efficacy as an agonist of this receptor as Ariadne, but has 12- to 16-fold higher activational potency in comparison.^[3] Like Ariadne, 4C-I produces an attenuated head-twitch response relative to the psychedelic drug DOPR, with a similar maximal response as Ariadne.^[3] The chemical synthesis of 4C-I has been described.^[1]^[5]^[6]^[3] 4C-I first described in the scientific literature by Alexander Shulgin and colleagues in 1977.^[5]^[6] Subsequently, it was described in greater detail by Michael Cunningham and colleagues in 2023.^[3]

References

1 2 3 4 Shulgin A, Shulgin A (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California: Transform Press. ISBN 0-9630096-0-5. OCLC 25627628. "Many, many analogues of ARIADNE have been made, and for a variety of reasons. In the industrial world there is research backup carried out, not only for the discovery of new things, but also for patent protection of old things. Several dozen analogues of ARIADNE have been made and pharmacologically evaluated, and some of them have been put into the published literature. The major points of variation have been two: keep the 4-position methyl group intact, and make the variations on the alpha-carbon (propyl, butyl, dimethyl, phenyl, benzyl, phenethyl, etc.—an extensive etc.) or: keep the alpha-position ethyl group intact and make the variations on the 4-position (chloro, iodo, methylthio, carboxy, etc.—again, an extensive etc.)." [...] "The four-carbon butylamine homologue (the ARIADNE analogue) of DOI has been synthesized. A mixture of the free base of 1-(2,5-dimethoxyphenyl)-2-aminobutane (see preparation under DOB) and phthalic anhydride was fused, cooled, and recrystallized from either methanol or cyclohexane to give crystals of N-[1-(2,5-dimethoxyphenyl)-2-butyl]phthalimide with a melting point of 76–77 °C and an analysis (C20H21NO4) C,H,N. This was iodinated with iodine monochloride in acetic acid to give N-[1-(2,5-dimethoxy-4-iodophenyl)-2-butyl]phthalimide which was chromatographically distinct from the uniodinated starting material (silica gel, CH2Cl2 ), but which did not crystallize. This was treated with hydrazine hydrate in ethanol to provide 1-(2,5-dimethoxy-4-iodophenyl)-2-aminobutane hydrochloride which was crystallized from CH3CN/EtOH to give white crystals with a mp of 217–218.5 °C and an analysis (C12H19CINO2) C,H,N. This butyl homolog of DOI has been assayed at up to four milligrams, and is without any central effects whatsoever. An experiment with 12.4 microcuries of 131I labelled material with the whole body scanner showed most of it accumulating in the gut and liver, with almost none to the brain."
1 2 3 4 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. 832. ISBN 978-3-03788-700-4. OCLC 858805226. Archived from the original on 21 August 2025.
1 2 3 4 5 6 7 Cunningham MJ, Bock HA, Serrano IC, Bechand B, Vidyadhara DJ, Bonniwell EM, et al. (January 2023). "Pharmacological Mechanism of the Non-hallucinogenic 5-HT_2A Agonist Ariadne and Analogs". ACS Chemical Neuroscience. 14 (1): 119–135. doi:10.1021/acschemneuro.2c00597. PMC 10147382. PMID 36521179.
↑ Shulgin A, Manning T, Daley PF (2011). The Shulgin Index, Volume One: Psychedelic Phenethylamines and Related Compounds. Vol. 1. Berkeley, CA: Transform Press. p. 341. ISBN 978-0-9630096-3-0. OCLC 709667010.
1 2 Braun U, Shulgin AT, Braun G, Sargent T (December 1977). "Synthesis and body distribution of several iodine-131 labeled centrally acting drugs". Journal of Medicinal Chemistry. 20 (12): 1543–1546. doi:10.1021/jm00222a001. PMID 592317.
1 2 Standridge RT, Howell HG, Tilson HA, Chamberlain JH, Holava HM, Gylys JA, et al. (February 1980). "Phenylalkylamines with potential psychotherapeutic utility. 2. Nuclear substituted 2-amino-1-phenylbutanes". Journal of Medicinal Chemistry. 23 (2): 154–162. doi:10.1021/jm00176a010. PMID 7359529.

References

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