Examples of partial lysergamides that are simple tryptamines include N-DEAOP-NMT and 5-MeO-N-DEAOP-NMT and examples that are simple phenethylamines include N-DEAOP-NMPEA and 25D-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, are 2-aminotetralins. Others, like NDTDI and LY-178210, are tricyclic compounds that still contain both tryptamine and phenethylamine components. Tochergamine is a simplified analogue of ergometrine that was clinically investigated as an oxytocic agent but was abandoned.
^ abShulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN978-0-12-290559-9. 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.
^Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144 (128). ISBN978-0-85608-011-1. OCLC2176880. OL4850660M. Archived from the original on 2025-05-27. Retrieved 2025-06-02. 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).
^Euvrard, Catherine; Ferland, Louise; Fortin, Michel; Oberlander, Claude; Labrie, Fernand; Boissier, Jacques R. (1981). "Dopaminergic activity of some simplified ergoline derivatives". Drug Development Research. 1 (2): 151–161. doi:10.1002/ddr.430010208. ISSN0272-4391.
^Plieninger, Hans (1953). "Die Synthese von Modellsubstanzen für die Lysergsäure I. Mitteilung". Chemische Berichte. 86 (1): 25–31. doi:10.1002/cber.19530860106. ISSN0009-2940. Retrieved 2 June 2025. 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 kristallisierenden tert. 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.
^Horii Z, Kurihara T, Yamamoto S, Ninomiya I (November 1967). "Studies on ergot alkaloids and related compounds. XIV. Synthesis of N-alkyl-4-methyl-2,3,4,4a,5,6-hexahydrobenzo[f]quinoline-2-carboxamides and stereochemistry of diethyl 4-methyl-1-oxo-1,2,3,4,4a,5,6,10b-octahydro-benzo[f]quinoline-2,2-dicarboxylate". Chem Pharm Bull (Tokyo). 15 (11): 1641–1650. doi:10.1248/cpb.15.1641. PMID5583819. 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)—[...]
^Norris PE, Blicke FF (December 1952). "Potential ergot substitutes: esters and amides of beta-amino acids". J Am Pharm Assoc Am Pharm Assoc. 41 (12): 637–639. doi:10.1002/jps.3030411204. PMID13022416. 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).
^"PiHKAL·info". DOM-NDEPA. 28 February 2025. Retrieved 24 March 2025.
^Marini-Bettolo, G. B., Chiavarelli, S., & Bovet, D. (1951). Synthetic Sympatholytic Substances of the Ergotamine Series. I. Nitrogen-Substituted Derivatives of the dl-1, 2, 3, 4-Tetrahydro-2-Naphthylamine-Containing Amino and Amido Functional Groups. Gazz. Chim. Ital, 80, 281–298. https://scholar.google.com/scholar?cluster=2759784031777399013
^"PiHKAL·info". search. 26 February 2025. Retrieved 24 March 2025.
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