Phenethylamine derivatives

Winter, J.C. Effects of the phenethylamine derivatives BL-3912, fenfluramine, and Seh-12679, in rats trained with LSD as a discriminative stimulus. Psychopharmacology 68 159-162, 1980. 

Zopf, D.A., Smith, D.F., Drzeniek, Z., Tsai, C.-M., and Ginsburg, V. (1978a) Affinity purification of antibodies using oligosaccharide-phenethylamine derivatives coupled to Sepharose. In Methods in Enzymology, (V. Ginsburg, ed.), Vol. 50, pp. 171-175. Academic Press, New York. 

FIG. 1. Illustration of a proposed hydrophobic surface, normal to the plane of the aromatic ring, which can accommodate lipophilic 4-substitutents in 3,4,5-trisubstituted phenethylamine derivatives. 

The 2-phenylcyclobutylamines Structures 14 and 15 have also been prepared (161). In contrast to the cyclopropylamine, however, 15 showed no clinical activity following oral administration of a dose up to 25 mg of the racemic hydrochloride (199). The trimethoxy congener 14 has not been tested. The appropriately ring-substituted tran.s-2-phenylcyclopentyl or cyclohexylamines have not been reported. Based on the apparent lack of activity for 15, as well as the lack of activity for alpha-ethyl phenethylamine derivatives, however, these might be predicted to be inactive. 

While mescaline is a simple 2-phenethylamine derivative, the addition of an alpha-methyl group to the side chain yields Structure 8 (TMA). This simple hybrid of the structures of mescaline and amphetamine retains the hallucinogenic effects of mescaline but possesses about twice the potency of the latter (174,200). Addition of the alpha-methyl to other 3,4,5-substituted compounds generally brings about an approximately twofold increase in potency. The addition of an alpha-methyl to 2,4,5-substituted compounds, however, may dramatically increase activity. For example, 2-(2,4,5-trimethoxyphenyl) ethylamine apparently is clinically inactive (195). Addition of an alpha-methyl gives TMA-2 (Table 1), with 20 times the potency of mescaline. However, the addition of an alpha-methyl does not significantly increase in vitro receptor affinity in either 3,4,5-or 2,4,5-series (72,78). Thus it is probable that the alpha-methyl may confer metabolic stability in vivo. It could also be speculated that this protection is more important in the 2,4,5-substituted series than in 3,4,5-substituted compounds. 

Reactions Catalyzed by Complexes of Bis-Phenethylamine-Derived Pbospboramidite, LI... 

An analogous strategy, using a chiral phenethylamine derivative, was followed by Leg-seir et al. 133) in a synthesis of tubotaiwin. 

Brand IMame(s) Tenuate, Tenuate Dospan Chemical Class Phenethylamine derivative... 

Improvements in the traditional aryl C-1 cyclization reaction were reported (Scheme 11). Generally, condensation reactions of phenethylamine derivatives do not perform well with electron-withdrawing groups. Reaction of sulfamoyl- 3-phenethylamines 46, even containing an aryl nitro group, with chloro(methylthio)acetate <99H(51)103> or a-... 

There are two main chemical categories of hallucinogens the indolealkylamine derivatives, wh ich are related to theneurotrans-mitter serotonin, and the phenethylamine derivatives, which... 

Finkle et al. (46) have established a GC/MS reference data system for the identification of drugs of abuse. The data include phenethylamine derivatives, opiate and synthetic narcotics, barbiturates, and urinary metabolites. These data have been established for use with the gas chromatographic retention time index previously developed. 

If a drug has been initially developed (and initially named) as an amphetamine derivative (three carbon chain) then the two-carbon chain analogue will use the original name (or a symbolic part of it) with the term 2C ahead of it. The two-carbon analogue of DOB (a three-carbon chain compound) will become 2C-B. DOI becomes 2C-I, DON becomes 2C-N, and DOET becomes 2C-E. Each of these is a substituted amphetamine derivative lacking one carbon atom, thus becoming a phenethylamine derivative. Most of these have 2,4,5-substitution patterns. 

M. A. Shaw and H. W. Peel, Thin-layer chromatography of 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and other phenethylamine derivatives, J. Chromatogr., 104 201 (1975). 

The most well known of the naturally occurring phenethylamine derivatives (Table I) are the transmitters of the sympathetic nervous system, epinephrine, norepinephrine, and dopamine. All these compounds are 3,4-dioxygenated in the aromatic nucleus and are collectively known as the catecholamines. Norepinephrine is the transmitter of most sympathetic postganglionic fibers, dopamine is the predominant transmitter of the mammalian extrapyramidal system and of several mesocortical and mesolimbic neuronal pathways, and epinephrine is the major hormone of the adrenal medulla (363). The literature that has accumulated on the action of these compounds in higher animals is enormous. Metanephrine and normetanephrine are known from animals as deactivated metabolites of epinephrine and norepinephrine that result from the action of the enzyme catechol O-methyltransferase (364). 

The Pd-catalyzed cyclization of appropriate 2-phenethylamine derivatives is a commonly used approach to the isoquinoline system as illustrated by Scheme 111 <2002JOC465, CHEC-III(7.05.2.1)234>. 

Vol. L [14]. Carbohydrate Antigens Coupling of Oligosaccharide-Phenethylamine Derivatives to Edestin by Diazotization and Characterization of Antibody Specificity by Radioimmunoassay. D. A. Zopf, C.-M. Tsai, and V. Ginsburg. 

The isoquinoline alkaloids are the second largest group of alkaloids, numbering about 6000, and can be viewed as five subgroups—the simple tetrahydroisoquinolines, the benzylisoquinolines, the phenethylisoquinolines, the Amaryllidaceae alkaloids, and the monoterpene isoquinolines. In addition, there are a number of simple phenethylamine derivatives, including ephedrine (originally from Ephedra species, but now synthesized) and pseudoephedrine, used for asthma and nasal... 

Nichols, D.E., Shulgin, A.T., and Dyer, D.C. Directional Lipophilic Character in a Series of Psychotomimetic Phenethylamine Derivatives. Life Sci, 21 569-576. 1977. 

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