Partial or simplified ergolines and lysergamides areanalogues ofergolines andlysergamides likeLSD in which one or moreatoms orbonds, for instance within theergolinering system, have been removed.[1][2][3][4] Additionalsubstitutions may also be added, for instance on the A ring of the ergoline nucleus.[1][2][3] It is notable that the ergoline ring system contains embeddedtryptamine andphenethylaminemoieties within itsstructure, and so some partial ergolines are simple tryptamines,cyclized tryptamines, simple phenethylamines, and/orcyclized phenethylamines.
In terms ofpharmacology, partial lysergamides includeserotonin anddopamine receptor agonists. Some, likeNDTDI,DEMPDHPCA,DEIMDHPCA, andLPH-5, areserotonin5-HT2A receptoragonists and havepsychedelic-like and/orpsychoplastogenic effects. Some, like8-OH-DPAT andLY-178210, areselective serotonin5-HT1A receptor agonists. Others, likerotigotine,nolomirole, andRU-28251, are dopamineD2-like receptor agonists. Partial ergolines have generally shown markedly reducedpotency in terms of hallucinogen-like effects compared to LSD.[5]
Examples of partial lysergamides that are simple tryptamines includeN-DEAOP-NMT and5-MeO-N-DEAOP-NMT and examples that are simple phenethylamines includeN-DEAOP-NMPEA and25D-NM-NDEAOP. An example of a cyclized tryptamine-like compound is DEIMDHPCA while examples of cyclized phenethylamines include DEMPDHPCA,DEMPDHPCA-2C-D, and LPH-5. Some, like 8-OH-DPAT and rotigotine, are2-aminotetralins. Others, like NDTDI and LY-178210, aretricyclic compounds that still contain both tryptamine and phenethylamine components.Tochergamine is a simplified analogue ofergometrine that was clinically investigated as anoxytocic agent but was abandoned.
| Structure | Name | Chemical name | CAS # |
|---|---|---|---|
 | NDTDI (8,10-seco-LSD) | N,N-diethyl-3-(methyl(1,3,4,5-tetrahydrobenzo[cd]indol-4-yl)amino)propanamide | |
 | RU-28251[6][7] | N,N-dipropyl-1,3,4,5-tetrahydrobenzo[cd]indol-4-amine | |
 | Bay R 1531 (LY-197206) | 1,3,4,5-tetrahydro-6-methoxy-N,N-dipropyl-benz[cd]indol-4-amine | 98770-54-8 |
 | LY-293284 | (4R)-6-acetyl-4-(di-n-propylamino)-1,3,4,5-tetrahydrobenz[c,d]indole | 141318-62-9 |
 | LY-178210 | 4-(dipropylamino)-1,3,4,5-tetrahydrobenzo[cd]indole-6-carboxamide | 114943-19-0 |
 | RU-28306 | N,N-dimethyl-1,3,4,5-tetrahydrobenzo[cd]indol-4-amine | 73625-11-3 |
 | FHATHBIN | 5-hydroxy-11-aminotetrahydrobenzindole | |
 | RU-27849 | 1,3,4,5-tetrahydrobenzo[c,d]indol-4-amine | 77963-70-3 |
 | N-DEAOP-NMT | N-(3-diethylamino-3-oxopropyl)-N-methyltryptamine | |
 | N-DEAOP-NET | N-(3-diethylamino-3-oxopropyl)-N-ethyl-5-tryptamine | |
 | N-DEAOP-5-MeO-NMT | N-(3-diethylamino-3-oxopropyl)-N-methyl-5-methoxytryptamine | |
 | N-DEAOP-5-MeO-NET | N-(3-diethylamino-3-oxopropyl)-N-ethyl-5-methoxytryptamine | |
 | 10,11-Seco-LSD[8] | 9,10-didehydro-N,N-diethyl-6-methyl-10,11-secoergoline-8β-carboxamide | |
 | CT-5252 | methyl-12-bromo-8,9-didehydro-2,3β-dihydro-6-methyl-10,11-secoergoline-8-carboxylate | |
 | 10,11-Secoergoline | 3-(piperidin-2-ylmethyl)-1H-indole | 5275-05-8 |
 | FAEFHI | 4-(2-aminoethyl)-1H-indol-5-ol | |
 | RU-27251 (3,5-secoergoline)[9] | 4-piperidin-3-yl-1H-indole | 16176-75-3 |
 | DEIMDHPCA | (3R)-N,N-diethyl-5-(1H-indol-4-yl)-1-methyl-3,6-dihydro-2H-pyridine-3-carboxamide | 2640392-28-3 |
 | WXVL_BT0793LQ2118 | 6-fluoro-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1H-indole | |
 | DEMPDHPCA ("compound 160a")[10][8] | N,N-diethyl-1-methyl-5-phenyl-3,6-dihydro-2H-pyridine-3-carboxamide | |
 | DEMPDHPCA-PMA ("compound 160b")[10] | N,N-diethyl-1-methyl-3-(4-methoxyphenyl)-1,2,5,6-tetrahydropyridine-5-carboxamide | |
 | DEMPDHPCA-mescaline ("compound 160c")[10] | N,N-diethyl-1-methyl-3-(3,4,5-trimethoxyphenyl)-1,2,5,6-tetrahydropyridine-5-carboxamide | |
 | DEMPDHPCA-NAP ("compound 160d")[10] | N,N-diethyl-1-methyl-3-(1-naphthyl)-1,2,5,6-tetrahydropyridine-5-carboxamide | |
_structure.png) | DEMPDHPCA-2C-D ("compound 45")[2] | 1-methyl-3-(1-oxo-1-diethylaminomethyl)-5-(2,5-dimethoxy-4-methylphenyl)-3,6-dihydro-2H-pyridine | |
.png) | "Compound XXIII"[3][11][12] | ? | ? |
 | LPH-5 | (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine | 2641630-97-7 |
.png) | "Compound 163" or "VIII"[10][13][14] | N,N-diethyl-4-methyl-2,3,4,4a,5,6-hexahydrobenzo(f)quinoline-2-carboxamide | |
 | N-DEAOP-NMPEA (PEA-NM-NDEPA)[15] | N-diethylaminocarbonylethyl-N-methylphenethylamine | |
 | 3,4-DMPEA-NDEPA | N-diethylaminocarbonylethyl-3,4-dimethoxyphenethylamine | |
 | DOM-NDEPA[16] | N-diethylaminocarbonylethyl-2,5-dimethoxy-4-methylamphetamine | |
 | DOB-NDEPA[17] | N-diethylaminocarbonylethyl-2,5-dimethoxy-4-bromoamphetamine | |
 | DOI-NDEPA[17] | N-diethylaminocarbonylethyl-2,5-dimethoxy-4-iodoamphetamine | |
 | DOTFM-NDEPA[17] | N-diethylaminocarbonylethyl-2,5-dimethoxy-4-trifluoromethylamphetamine | |
 | TMA-2-NDEPA[18] | N-diethylaminocarbonylethyl-2,4,5-trimethoxyphenethylamine | |
 | M-NDEPA (mescaline-NDEPA)[19] | N-diethylaminocarbonylethyl-3,4,5-trimethoxyamphetamine | |
 | 25D-NM-NDEAOP (25D-NM-NDEPA) | N-methyl-N-(3-diethylamino-3-oxopropyl)-2,5-dimethoxy-4-methylphenethylamine | |
 | 2-Aminotetralin | 1,2,3,4-tetrahydronaphthalen-2-amine | 2954-50-9 |
 | CHF-1024 | 5,6-dihydroxy-N-methyl-2-aminotetralin | 39478-89-2 |
 | Nolomirole (CHF-1035) | 5,6-diisobutyryloxy-N-methyl-2-aminotetralin | 90060-42-7 |
 | 5-OH-DPAT | 5-hydroxy-N,N-dipropyl-2-aminotetralin | 68593-96-4 |
 | 7-OH-DPAT | 7-hydroxy-N,N-dipropyl-2-aminotetralin | 74938-11-7 |
 | 8-OH-DPAT | 8-hydroxy-N,N-dipropyl-2-aminotetralin | 78950-78-4 |
 | UH-301 | (S)-5-fluoro-8-hydroxy-N,N-dipropyl-2-aminotetralin | 127126-22-1 |
 | UH-232 | (1S,2R)-5-methoxy-1-methyl-N,N-propyl-2-aminotetralin | 95999-12-5 |
 | Rotigotine | 6-[propyl(2-thiophen-2-ylethyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol | 99755-59-6 |
Simplified LSD analogues containing only the D ring, also known as the THPC series (1-N-methyl-1,2,5,6-tetrahydropyridine-3-N,N-diethylcarboxamide) and related compounds, have also been described.[20] They appear to act asserotonin andpsychedelic antagonists inpreclinical research.[20]
| Structure | Name | Chemical name | CAS # |
|---|---|---|---|
 | Chanoclavine (chanoclavine-I) | [9(9a)E]-9-methyl-9,9a-didehydro-7,8-seco-9a-homoergolin-8-ol | 2390-99-0 |
 | Chanoclavine II | (2E)-2-methyl-3-[(4R,5S)-4-(methylamino)-1,3,4,5-tetrahydrobenzo[cd]indol-5-yl]prop-2-en-1-ol | 1466-08-6 |
 | Paliclavine | (9R)-6,8-dimethyl-7,8-didehydro-6,7-secoergolin-9-ol | 52052-66-1 |
 | 2C-B-5-hemiFLY-α6 | 8-bromo-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1,8-bc]furan-4-amine | ? |
 | 2C-B-morpholine | 2-(4-bromo-2,5-dimethoxyphenyl)morpholine | 807631-07-8 |
 | Naxagolide | (4aR,10bR)-4-propyl-2,3,4a,5,6,10b-hexahydrobenzo[h][1,4]benzoxazin-9-ol | 88058-88-2 |
-Quinagolid_Structural_Formula_V1.svg) | Quinagolide | N,N-diethyl-N-[(3S,4aS,10aR)-6-hydroxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g]quinolin-3-yl]sulfamide | 87056-78-8 |
 | 25B-NAcPip | N-(piperidin-1-ylcarbonylmethyl)-4-bromo-2,5-dimethoxyphenethylamine | |
_structure.png) | "Compound 37"[21][2][22] | N-(2-diethylamino-2-oxoethyl)-N-methyl-2-amino-1,2,3,4,4a,8a-hexahydronaphthalene | |
 | Tochergamine | N,N-diethyl-2-(1,2,3,4-tetrahydronaphthalen-1-ylamino)acetamide |
The largest number of structural analogs of LSD that have been prepared involve the opening of one or more of the rings of the parent lysergic acid system. The compounds with the piperidine ring (ring D) opened [see (I)] are encountered as natural products in the several Convolvulaceae discussed in Section II,B on ololiuqui. The opening of ring C (by cleavage of the 10-11 bond to the indole "4 position") results in a series of N-α-disubstituted tryptamines. Additionally, analogs are known with the indolic nitrogen replaced with sulfur (benzothiophenes) and with an aliphatic chain (tetralins). A recent review covers this chemistry (Campaigne and Knapp, 1971), but there is apparently no human psychopharmacology as yet known.
Various attempts to simplify the LSD structure by breaking it down into molecular fragments have, with the exception of the tryptamines, generally led to profoundly deleterious effects on the hallucinogenic activity (Campaigne and Knapp, 1971).
Table 1. Human psychotomimetic potencies of LSD analogs. [...]
Die Synthese der 1.6-Dimethyl-5-[4-methoxy-phenyl]-pyridin- carbonsäure-(3), ihres Tetrahydro- und Hexahydro-Derivates, sowie einer Reihe anderer uterusaktivor Amine Wird beschrieben. [...] Da die Verbindungen V und VI auf den Kaninchenuterus in situ auch nur eine verhaltnismäßig schwache Wirkung ausüben, wurde versucht, der LysergsäureeKonstitution näherzukommen. Bekanntlich tritt bei den hydrierten Mutterkornalkaloiden die Uteruswirkung zugunsten der sympaticolytischen Wirkung zurück. In der Annahme, daß die Uteruswirksomkeit auch bei unseren Modellsubstanzen durch die Doppelbindung in 3.4-Stellung gesteigert wird, haben wir die Verbindung XIV und XV nach dem folgenden Formelschema synthetisiert. Vorher hotten wir vergeblich versucht, die Pyridine Verbindung X bzw. ihr Methosulfat partiell zu hydrieren. [...] Die Einwirkung von p-Methoxy-phenyl-magnesiumbromid11) auf einen Überschuß an Ketoester führt zu dem nicht kristallisierendentert. Alkohol XIV, wobei die größere. Reaktionsfähigkeit der Ketogruppe gegenüber der Estergruppe ausgenützt wird. Durch Wasserabspaltung mittels Thionylchlorids in Pyridin12) erhält man in mäßiger Ausbeute ein schön kristallisiertes Oxalat der Formel XV bzw. XVI. Eine Entscheidung, in welcher Richtung die Wasserabspaltung erfolgt ist, steht vorläufig noch aus. Die Verbindung zeigte sich in ihrer pharmakologischen Wirkung den gesättigten Derivaten V und VI deutlich überlegen.
Our previous report1) introduced the synthesis of a potent oxytocic ethyl 4-methyl-2,3,4,4a,5,6-hexahydrobenzo[f]quinoline-2-carboxylate (VII). Recently, Ohta and his coworkers also prepared V] by a convenient method starting from the Mannich product (II). However, they did not deal with the stereochemistry of the compounds involved. In the course of work searching for compounds with potent activity related to lysergic acid, we now wish to describe two routes of preparations of diethyl-, n-butyl- and 2-hydroxyisopropylamide derivatives of VI, which can be regarded as LSD25 analogs lacking only a pyrrole ring, and also discuss the stereochemistry of this series of compounds. [...] Of these amide derivatives, the diethylamide (VIII) was also prepared by an alternative route as follows. [...] Experimental. [...] N,N-Diethyl-4-methyl-2,3,4,4a,5,6-hexahydrobenzo(f)quinoline-2-carboxamide (VIII)—[...]
Six esters and amides of derivatives of β-alanine which are related to lysergic acid have been prepared and tested for oxytocic activity. None of these products possess a significant oxytocic activity. [...] The purpose of this investigation was to synthesize amides and also esters of compounds (II–V) which represent fragments of the lysergic acid molecule in the hope that some of these products might possess oxytocic activity. Various modified fragments of the lysergic acid molecule have been synthesized previously; it was claimed that some of the compounds are active oxytocics (1—7). [...] Pharmacologic data indicated that none of the esters or amides of compounds II—V which were prepared possess a significant oxytocic action when compared to the clinically used oxytocics. However, the diethylamide of N-methyl-N-[β′-(3-indolyl)-ethyl]-β-alanine (IIIc) appeared to have an oxytocic activity approximately ten times stronger than that of the diethylamide of N-methyl-N-(β′-phenethyl)-β-alanine (IIc).
Table 3. New phenylalkylamine and tryptamine congeners. Cf. also Figure 5. [...] Figure 5. Molecular structures of the new 5-HT2A congeneric ligands. Cf. also Table 3. [...] Table 4. Predicted binding affinities of new compounds, index by substance classes. [...]