Tryptamines structure-activity relationship

Perhaps the advantage of the medicinal chemistry route lies in the flexibility of introducing different alkyl groups on the primary amine through reductive amination on 2-aminoethyl indole 10 and hence allows access to various N, N-dialkyl tryptamine derivatives for structure-activity relationship (SAR) studies. 

Compounds such as LSD or the beta-carbolines do not possess a primary amino group, are not rapidly metabolized in comparison to, for example, tryptamine, and enter the brain readily certain substituent groups can alter this situation. Members of the phenylalkylamine and indolealkylamine families of hallucinogens can produce similar effects in animals but may be capable of producing distinctive effects in man. As yet, there is no satisfactory and comprehensive structure-activity relationship that encompasses both major classes of compounds. This may be due in part to unique metabolic and distributional characteristics associated with the individual ring systems. 

Gessner, P. K., Godse, D. D., Krull, A. H., and McMullan, J. M. (1968) Structure-activity relationships among 5-methoxy-N,N-dimethyltryptamine, 4-hydroxy-N,N-dimethyltryptamine (psilocin) and other substituted tryptamines. Life Sci., 7 267-277. 

These are the exact rings. They are easy to make they add a sense of sophistication to an otherwise pedestrian scientific paper and they often represent the inactive extremes in a receptor site study of a structure activity relationship study of a CNS-active agent. But the compounds represented here appear to have simply the wrong properties, somehow, and should not really be seriously considered in the quest for understanding of the remarkable actions of most of the psychedelic phenethylamines and tryptamines. 

The discovery that tryptamine is also an endogenous enhancer substance (Knoll 1994) opened the way for a structure-activity relationship study aiming to synthesize a new family of enhancer compounds structurally unrelated to PEA and the amphetamines. J -(-)-l-(benzofuran-2-yl)-2-propylaminopen-tane [ (-)-BPAP ] was selected as a tryptamine-derived synthetic mesencephalic... 

The activity of some tryptamine derivatives as MAOIs has been investigated (Ho et al. 1970 Lessin, Long 8c Parkes 1967 Barlow 1961). Unlike the carbo-lines, however, extensive studies of the structure-activity relationships of tryptamines with respect to MAOI activity have not been carried out. Lessin, Long Parkes (1967) examined the structure-activity relationships of a series of substituted tryptamines and 0-carbolines on... 

Johnson, M.P., Loncharich, R.J., Baez, M. and Nelson, D.L. (1994) Species variations in transmembrane region V of the 5-hydroxytryptamine type 2A receptor alter the structure-activity relationship of certain ergolines and tryptamines. Mol. Pharmacol., 45,277-286. 

Although the available literature indicates that MAOIs do have agnificant influences on both the metabolism and behavioral effects of DMT, apparently the specific interactions of DMT with 3-carbolines have not been investigated. This apparent oversight is especially remarkable in view of the close structural relationships of tryptamine derivatives and arbolines (see Tables 1 and II), the probable metabolic interconversion of DMT, other tryptamines and /J-carbolines (Barker, Monti 8c Christian 1980 Hsu 8c Mandell 1975), the involvement of both classes of compounds in important neuroregulatory functions such as MAO activity and... 

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