5C-D

5C-D, also known as 4-methyl-2,5-dimethoxy-α-propylphenethylamine, is a putatively non-hallucinogenic serotonin 5-HT₂ receptor agonist of the phenethylamine and α-propylphenethylamine families related to the 4C drug Ariadne (4C-D).^[1][2]

5C-D

Clinical data
Other names	4-Methyl-2,5-dimethoxy-α-propylphenethylamine; 2,5-Dimethoxy-4-methyl-α-propylphenethylamine; α-Propyl-Ariadne; 5C-DOM; α-Propyl-2C-D
Drug class	Serotonin 5-HT2 receptor agonist
ATC code	None
Identifiers
IUPAC name 1-(2,5-dimethoxy-4-methylphenyl)pentan-2-amine
PubChem CID	171417407
Chemical and physical data
Formula	C14H23NO2
Molar mass	237.343 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCCC(CC1=C(C=C(C(=C1)OC)C)OC)N
InChI InChI=1S/C14H23NO2/c1-5-6-12(15)8-11-9-13(16-3)10(2)7-14(11)17-4/h7,9,12H,5-6,8,15H2,1-4H3 Key:VZEDHPXICDLLDV-UHFFFAOYSA-N

At the serotonin 5-HT_2A receptor, 5C-D is a potent and higher-efficacy partial agonist, with an EC₅₀Tooltip half-maximal effective concentration of 291 nM and an E_maxTooltip maximal efficacy of 69%.^[1][2] It is about half as potent as Ariadne as a serotonin 5-HT_2A receptor agonist and has about 15% lower efficacy in activating the receptor in comparison.^[1][2] 5C-D has also been shown to be a serotonin 5-HT_2B receptor agonist.^[2] In contrast to Ariadne and serotonergic psychedelics, 5C-D does not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents.^[2]

5C-D was first described in the scientific literature by Michael Cunningham and colleagues by 2023.^[2] It was synthesized and assessed during structure–activity relationship (SAR) studies of Ariadne.^[1][2]

See also

• Substituted methoxyphenethylamine
• 4C and Ariadne (4C-D)

References

1. Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chemical Reviews. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123. As mentioned earlier, the potency and efficacy would be weakened if the methyl group on the α-postion of DOM (EC50 = 36.9 nM, Emax = 96.6%) is replaced with an ethyl group (95, ariadne, EC50 = 182 nM, Emax = 79.1%) in the Gq-dissociation BRET assay, and further reduced with an n-propyl group (137, 5C-D, EC50 = 291 nM, Emax = 68.8%).173 These results demonstrated that the length of the alkyl substituent at this position is related to compound activity at the 5-HT2AR.
2. Cunningham MJ, Bock HA, Serrano IC, Bechand B, Vidyadhara DJ, Bonniwell EM, et al. (January 2023). "Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs". ACS Chemical Neuroscience. 14 (1): 119–135. doi:10.1021/acschemneuro.2c00597. PMC 10147382. PMID 36521179. Furthermore, the α-propyl analog (compound 5C-D) showed an additional decrease in potency (∼2-fold) and efficacy (∼15 % drop) relative to Ariadne (Figure 3D). [...] Also, α-propyl-Ariadne (5C-D) induced HTR response that is indistinguishable from vehicle (Figure S13). [...]

External links

• 5C-D - Isomer Design