4-PhPr-2,5-DMA

Pharmaceutical compound From Wikipedia, the free encyclopedia

4-(3-Phenylpropyl)-2,5-dimethoxyamphetamine (DOPP or DOPhPr), also known as 4-PhPr-2,5-DMA, is a serotonin receptor modulator of the phenethylamine, amphetamine, and DOx families.^[1]^[2]^[3]^[4]^[5]^[6]^[7] The properties and effects of 4-PhPr-2,5-DMA in humans do not appear to be known.^[1] It shows high affinity for both the serotonin 5-HT_2A and 5-HT_2C receptors and acts as a weak partial agonist or antagonist of the serotonin 5-HT_2A receptor.^[7]^[5]^[6] The drug has lower affinity for the serotonin 5-HT_2A receptor than its closely related positional isomer 4-PhPr-3,5-DMA.^[7] This is an apparent reversal of the usual situation with DOx and related drugs, in which the 2,5-dimethoxy pattern is optimal for serotonin 5-HT_2A receptor interactions.^[7] 4-PhPhr-2,5-DMA was first described in the scientific literature by Richard Glennon and colleagues by 1989.^[8]^[9]^[6]

Other names4-(3-Phenylpropyl)-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-(3-phenylpropyl)amphetamine; 4-PP-2,5-DMA; DOPP; DOPhPr; DOPh3

Routes of
administrationUnknown^[1]

Drug classSerotonin receptor modulator; Serotonin 5-HT_2A receptor partial agonist

ATC code

None

Quick facts Clinical data, Other names ...

4-PhPr-2,5-DMA
Clinical data

Other names	4-(3-Phenylpropyl)-2,5-dimethoxyamphetamine; 2,5-Dimethoxy-4-(3-phenylpropyl)amphetamine; 4-PP-2,5-DMA; DOPP; DOPhPr; DOPh3
Routes of administration	Unknown^[1]
Drug class	Serotonin receptor modulator; Serotonin 5-HT_2A receptor partial agonist
ATC code	None
Pharmacokinetic data
Duration of action	Unknown^[1]
Identifiers
IUPAC name 1-[2,5-dimethoxy-4-(3-phenylpropyl)phenyl]propan-2-amine
PubChem CID	44265227
ChemSpider	23108650
ChEMBL	ChEMBL8334
Chemical and physical data
Formula	C₂₀H₂₇NO₂
Molar mass	313.441 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(CC1=C(C=C(C(=C1)OC)CCCC2=CC=CC=C2)OC)N
InChI InChI=1S/C20H27NO2/c1-15(21)12-18-14-19(22-2)17(13-20(18)23-3)11-7-10-16-8-5-4-6-9-16/h4-6,8-9,13-15H,7,10-12,21H2,1-3H3 Key:XKCYCNKOOGOHIQ-UHFFFAOYSA-N

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. pp. 283–284, 775–776, 781. ISBN 978-3-03788-700-4. OCLC 858805226. Archived from the original on 21 August 2025.
[2]
Nichols DE (2012). "Structure–activity relationships of serotonin 5-HT2A agonists". Wiley Interdisciplinary Reviews: Membrane Transport and Signaling. 1 (5): 559–579. doi:10.1002/wmts.42. ISSN 2190-460X. Very large bulky groups at the 4-position, such as the tert-butyl, lead to inactive compounds,16,71–74 although the 4-isopropyl compound DOIPr is reported to retain good human activity.16 Not surprisingly, therefore, aryl groups attached at the 4-position gave antagonists, generally with low affinity.75 Interestingly, however, when a 3-phenylpropyl substituent was introduced at this position, the compound proved to be a weak partial agonist.76
[3]
Nichols DE (2018). Chemistry and Structure-Activity Relationships of Psychedelics. Current Topics in Behavioral Neurosciences. Vol. 36. pp. 1–43. doi:10.1007/7854_2017_475. ISBN 978-3-662-55878-2. PMID 28401524. Large bulky alkyl groups at the 4-position, such as isopropyl or tert-butyl, lead to inactive compounds (Glennon et al. 1981, 1982a; Glennon and Rosecrans 1982; Oberlender et al. 1984). Not surprisingly, therefore, aryl groups attached at the 4-position also gave antagonists, generally with low affinity (Trachsel et al. 2009). Interestingly, however, when a 3-phenylpropyl substituent was introduced at this position, the compound was reported to be a weak partial agonist (Dowd et al. 2000).
[4]
Trachsel D, Nichols DE, Kidd S, Hadorn M, Baumberger F (May 2009). "4-aryl-substituted 2,5-dimethoxyphenethylamines: synthesis and serotonin 5-HT(2A) receptor affinities". Chemistry & Biodiversity. 6 (5): 692–704. doi:10.1002/cbdv.200800235. PMID 19479848. Usually, compounds of structure 2 bearing a small lipophilic substituent at the crucially important 4'-position possess agonist behavior (Y¼halogen, Me, CF3, etc.), whereas those having a large lipophilic substituent (Y¼alkyl chainC4, 3-phenylpropyl, etc.) have antagonist activity [11], but to date the transition between these structures is not well-defined. [...] One may argue that a simple 4'-phenyl substituent in 2-phenylethylamines is still not large enough to allow full interaction with an 'antagonistic binding site' in the 5- HT2A receptor, and that its steric bulk exceeds a limited space in the agonistic binding site. As soon as a further substituent is introduced, (especially) in the para-position of the second arene moiety, antagonistic binding increases dramatically, a conclusion that completely agrees with the results of Glennon and co-workers [11] [32]: i.e., as soon as larger 4'-alkyl or 4'-arylalkyl substituents are introduced into 2-phenylethylamines, the compounds behave as antagonists. [...] Until recently, it was thought that the 2',5'-(MeO)2 pattern was required for high affinity of phenethylamines at the serotonin 5-HT2A receptor (reviewed in [11]). Although this pharmacophore may be necessary for agonist action, assumed to be the primary pharmacology of hallucinogenic phenethylamines [36] [37], Glennon and coworkers [11] [32] have shown that this substitution pattern is not required for high-affinity antagonists such as 13–15. [...] Fig. 2. Influence of structural modifications upon binding affinities towards 5-HT2 receptors (unless otherwise indicated, Ki values were taken from [11] and [32]). a) Values taken from [2]. The values given in parentheses are more recent [11]; nevertheless, the prior Ki values were used for a consistent comparison. b) This work.
[5]
Glennon RA, Dukat M (June 2024). "1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI): From an Obscure to Pivotal Member of the DOX Family of Serotonergic Psychedelic Agents - A Review". ACS Pharmacology & Translational Science. 7 (6): 1722–1745. doi:10.1021/acsptsci.4c00157. PMC 11184610. PMID 38898956.
[6]
Glennon RA, Teitler M, Sanders-Bush E (1992). "Hallucinogens and serotonergic mechanisms" (PDF). NIDA Research Monograph. 119: 131–135. PMID 1435968. Archived from the original (PDF) on August 5, 2023.
[7]
Dowd CS, Herrick-Davis K, Egan C, DuPre A, Smith C, Teitler M, et al. (August 2000). "1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT(2A) partial agonists". Journal of Medicinal Chemistry. 43 (16): 3074–3084. doi:10.1021/jm9906062. PMID 10956215.
[8]
Glennon RA, Seggel MR (November 1989). "Interaction of phenylisopropylamines with central 5-HT2 receptors. Analysis by quantitative structure-activity relationships.". Probing Bioactive Mechanisms. ACS Symposium Series. Vol. 413. pp. 264–280. doi:10.1021/bk-1989-0413.ch018. ISBN 978-0-8412-1702-7.
[9]
Seggel MR, Yousif MY, Lyon RA, Titeler M, Roth BL, Suba EA, et al. (March 1990). "A structure-affinity study of the binding of 4-substituted analogues of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors". Journal of Medicinal Chemistry. 33 (3): 1032–1036. doi:10.1021/jm00165a023. PMID 2308135.

4-PhPr-2,5-DMA

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