DEMPDHPCA-2C-D

DEMPDHPCA-2C-D
Clinical data
Other names	2C-D-DEMPDHPCA; "Compound 45"
Drug class	Possible serotonergic psychedelic or hallucinogen
ATC code	None;
Identifiers
	IUPAC name N,N-diethyl-1-methyl-5-(2,5-dimethoxy-4-methylphenyl)-3,6-dihydro-2H-pyridine-3-carboxamide;
Chemical and physical data
Formula	C20H30N2O3
Molar mass	346.471 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCN(CC)C(C1C=C(C2=CC(OC)=C(C)C=C2OC)CN(C)C1)=O;
	InChI InChI=1S/C20H30N2O3/c1-7-22(8-2)20(23)16-10-15(12-21(4)13-16)17-11-18(24-5)14(3)9-19(17)25-6/h9-11,16H,7-8,12-13H2,1-6H3; Key:ZANDNBLJKNVGIE-UHFFFAOYSA-N;

DEMPDHPCA-2C-D is a possible serotonergic psychedelic of the phenethylamine and 2C families.^[1] It is a cyclized phenethylamine and a partial or simplified lysergamide.^[1] More specifically, the compound is a derivative of 2C-D in which the β position has been cyclized with the amine to form a pyridine ring, an LSD-like N,N-diethylcarboxamide moiety has been added to the pyridine ring, and an N-methyl group has been added to the amine.^[1] Alternatively, it may be viewed as an analogue of LSD in which the atoms at positions 1 through 4 of the ergoline ring system have been removed and 4-methyl and 2,5-dimethoxy substitutions have been added to the phenyl ring (i.e., the A ring of LSD).^[1]

DEMPDHPCA-2C-D was synthesized and described by David E. Nichols in his thesis in 1973.^[1] Its pharmacology was not reported.^[1] However, several close analogues of DEMPDHPCA-2C-D, such as DEMPDHPCA and a few of its derivatives, have been reported to be potent serotonin 5-HT_2A receptor agonists^[2] or to produce hallucinogen-like behavioral effects in animals.^[3] In addition, the established putative psychedelic LPH-5 is very similar to DEMPDHPCA-2C-D in chemical structure but most notably lacks the LSD-like N,N-diethylcarboxamide moiety.^[4]^[5]

Chemical structures of DEMPDHPCA-2C-D and related compounds

2C-D
DEMPDHPCA
DEMPDHPCA-2C-D
LPH-5
LSD

References

^ ^a ^b ^c ^d ^e ^f ^g Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085. Part III. Proposed Synthesis of an LSD AD-Ring Congener To study the importance of the D ring of LSD it was proposed to prepare 45. This system presumably would possess a high HOMO as conferred on the system by the 2,5- dimethoxy-4-methyl substitution and is a close analog of LSD. [...]
^ WO 2021076572, Olson DE, Dunlap L, Wagner F, Chytil M, Powell NA, "Ergoline-like compounds for promoting neural plasticity", published 22 April 2021, assigned to Delix Therapeutics, Inc. and The Regents of the University of California
^ Mangner TJ (1978). Potential Psychotomimetic Antagonists. N,N -Diethyl-1-methyl-3-aryl-1,2,5,6-tetrahydropyridine-5-carboxamides (Ph.D. thesis). University of Michigan. doi:10.7302/11268. Archived from the original on 30 March 2025. The gross behavior of the test animals under the influence of 160a-d was observed during the course of the dose-response study depicted by Figure 7. The gross behavioral signs displayed by rats under the influence of the phenyl (160a) and trimethoxyphenyl (160c) homologs were indistinguishable from those exhibited with LSD, DMT or mescaline, and were characterized by general inactivity, muscle twitching and the occurrence of a Straub tail reaction (a somewhat specific indication of the influence of a psychotomimetic drug in which the tail is held in an upright 191 position ). The naphthyl homolog (160d) produced similar behavioral signs but the rats were more active than with 160a and 160c. The gross behavioral pattern of rats under the influence of the methoxy homolog (160b), in contrast, was not at all similar to that caused by LSD, 160a or 160c. It more closely resembled the pattern exhibited with amphetamine, characterized by very marked hyperactivity. [...] Initial indications, based on the gross behavioral comparisons mentioned previously, are that 160a,c,d possess psychotomimetic activity similar to LSD, while 160b possesses amphetamine-like stimulatory activity. [...] On the other hand, 160a, whose structure more closely resembles that of LSD, seems to have LSD-like activity of greater potency than either 160b or 160c. Since the structure of 160a is very closely related to the structure of LSD and contains no aryl methoxy groups necessary for psychotomimetic activity in the methoxyamphetamine series, it could be inferred that 160a acts via an LSD-like mechanism. [...] SUMMARY [...]
^ Gumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". British Journal of Pharmacology. doi:10.1111/bph.17361. PMID 39354889.
^ M Ro Rsted E, Jensen AA, Smits G, Frydenvang K, Kristensen JL (May 2024). "Discovery and Structure-Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists". Journal of Medicinal Chemistry. 67 (9): 7224–7244. doi:10.1021/acs.jmedchem.4c00082. PMC 11089506. PMID 38648420.

[Nichols_1973-1] ^ ^a ^b ^c ^d ^e ^f ^g Nichols DE (May 1973). Potential Psychotomimetics: Bromomethoxyamphetamines and Structural Congeners of Lysergic Acid (Thesis). University of Iowa. p. 23. OCLC 1194694085. Part III. Proposed Synthesis of an LSD AD-Ring Congener To study the importance of the D ring of LSD it was proposed to prepare 45. This system presumably would possess a high HOMO as conferred on the system by the 2,5- dimethoxy-4-methyl substitution and is a close analog of LSD. [...]

[WO2021076572-2] WO 2021076572, Olson DE, Dunlap L, Wagner F, Chytil M, Powell NA, "Ergoline-like compounds for promoting neural plasticity", published 22 April 2021, assigned to Delix Therapeutics, Inc. and The Regents of the University of California

[Mangner_1978-3] Mangner TJ (1978). Potential Psychotomimetic Antagonists. N,N -Diethyl-1-methyl-3-aryl-1,2,5,6-tetrahydropyridine-5-carboxamides (Ph.D. thesis). University of Michigan. doi:10.7302/11268. Archived from the original on 30 March 2025. The gross behavior of the test animals under the influence of 160a-d was observed during the course of the dose-response study depicted by Figure 7. The gross behavioral signs displayed by rats under the influence of the phenyl (160a) and trimethoxyphenyl (160c) homologs were indistinguishable from those exhibited with LSD, DMT or mescaline, and were characterized by general inactivity, muscle twitching and the occurrence of a Straub tail reaction (a somewhat specific indication of the influence of a psychotomimetic drug in which the tail is held in an upright 191 position ). The naphthyl homolog (160d) produced similar behavioral signs but the rats were more active than with 160a and 160c. The gross behavioral pattern of rats under the influence of the methoxy homolog (160b), in contrast, was not at all similar to that caused by LSD, 160a or 160c. It more closely resembled the pattern exhibited with amphetamine, characterized by very marked hyperactivity. [...] Initial indications, based on the gross behavioral comparisons mentioned previously, are that 160a,c,d possess psychotomimetic activity similar to LSD, while 160b possesses amphetamine-like stimulatory activity. [...] On the other hand, 160a, whose structure more closely resembles that of LSD, seems to have LSD-like activity of greater potency than either 160b or 160c. Since the structure of 160a is very closely related to the structure of LSD and contains no aryl methoxy groups necessary for psychotomimetic activity in the methoxyamphetamine series, it could be inferred that 160a acts via an LSD-like mechanism. [...] SUMMARY [...]

[Gumpper_2024-4] Gumpper RH, Nichols DE (October 2024). "Chemistry/structural biology of psychedelic drugs and their receptor(s)". British Journal of Pharmacology. doi:10.1111/bph.17361. PMID 39354889.

[RoRstedJensenSmits2024-5] M Ro Rsted E, Jensen AA, Smits G, Frydenvang K, Kristensen JL (May 2024). "Discovery and Structure-Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists". Journal of Medicinal Chemistry. 67 (9): 7224–7244. doi:10.1021/acs.jmedchem.4c00082. PMC 11089506. PMID 38648420.

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[2]

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[5]

DEMPDHPCA-2C-D

See also

References

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