Phenylethylamine, biological activities

Solid-phase library synthesis of triazolopyridazines via a [4+2] cycloaddition strategy has been accomplished <99TL619>. Intramolecular bis-Mannich reaction of 3-aryl-5-mercapto-13,4-triazole, formaldehyde and a-phenylethylamine yields chiral 5-aryltriazolo[3,4-ft]-[133]thiadiazine derivatives. These compounds have been screened for antibacterial activities and some of them show potent biological activity <99SC2027>. 

Figure 16.2 Dihydropyridine-pyridinium salt redox system for site-specific and sustained delivery to the brain. The prodrug A is delivered directly to the brain, where it is oxidized and trapped as the prodrug B. The quaternary ammonium salt is slowly cleaved by chemical/enzymatic action with sustained release of the biologically active phenylethylamine C and the facile elimination of the carrier molecule D. Elimination of the drug from the general circulation is by comparison accelerated, either as A or B or as cleavage products...

Biologically active derivatives of 2-phenylethylamine—adrenaline, noradrenaline, methamphetamine, mescaline, dopamine, fentanyl (a synthetic narcotic), and sumatriptan (Imitrex, a synthetic pain reliever) (Section 25.6C)... 

There are many components in chocolate. The biologically active stimulants are caffeine and theobromine. The amine compounds are tyramine and phenylethylamine or PEA. 

The pioneer work on the connexion between constitution and activity in the phenylethylamine series of sympathomimetic drugs was carried out by Barger and Dale (1910). It has since become clear that direct action of the hormone and neurotransmitter type, is strongest in examples with hydroxy-groups in the 3-and 4-positions of the benzene ring, i.e. the catecholamines such as norepinephrine, epinephrine and dopamine. The indirect action of examples without these embellishments has been outlined in Sections 9.4.3 (p. 358) and 7.6.3 (p. 300). As recounted in Section 12.1 the D-catecholamines (Fig. 12.1) have much more biological activity than their L-enantiomers. 

Biologically active substances have been linked to polyphosphates via ionic bonds between the substance and the polymer (Scheme 6.16). Troev and co-workers have reported the successful immobilization of drugs such as 2-phenylethylamine, cysteamine, and bendamustine hydrochloride, leading to enhanced stability and a lower cytotoxicity of the polymer-drug complexes than the pure analogs. 

Recent in vitro experiments have demonstrated the possibility that biologically active amines may be incorporated into the body protein. Using isotopes, it was shown that phenylethylamine, putrescine, histamine, cadaverine, colamine, methylamine, noradrenaline, and 5-hydroxytryptamine... 

The demonstration of a radioprotective effect for numerous biologically active amines in animal and in vitro experiments (phenylethylamine/ tyramine/ " N-methyl-p-octopamine (sympatol)/ 3-hydroxytyramine/ noradrenaline/... 

Biologically active derivatives of 2-phenylethylamine—adrenaline, noradrenaline, methamphetamine, mescaline,... 

Biologically active polyamines putrescine, spermidine and spermine, differ from the traditional group of biogenic amines. Spermidine and spermine arise under specific conditions and they also have different biological effects in comparison with the classical biogenic amines, which are mainly histamine, tyramine, 2-phenylethylamine, putrescine, cadaverine, tryptamine and agmatine. 

When the lithium enolate 84 is added to propenal (tvithout transmetala-tion), the diastereomeric esters 87a and 87b are formed in the ratio 92 8. In this reaction the crude mixture 87a/87b tvas hydrolyzed to give the carboxylic acid (R)-88 in 83.5% ee. To obtain the enantiomerically pure 3-hydroxy-4-pentenoic acid, enrichment tvas performed by single recrystallization of the ammonium salt, formed from (S)-l-phenylethylamine. When the amine has been liberated from the salt the carboxylic acid (R)-88 is obtained in >99.8% ee and 41% overall yield (Scheme 1.18) [132]. The (S) enantiomer, but not the ( R) enantiomer, of 3-hydroxy-4-pentenoic acid 88 (both prepared according to this procedure) has been sho vn to be a substrate for the enzyme 3-hydroxybutanoate dehydrogenase - another example of the different biological activity of enantiomeric compounds [133]. 

In the 1970s, Fuller examined the effects of jS,/f-difluoro substitution on the biological properties of a series of arylethylamines. Among the compounds prepared were p,p-difluoroamphetamine (19), )S,)S-difluoro phenethylamine (20), and A/-cyclopropyl-4-chloro-jS,jS-difluorophenylethylamine (21). A drop in amine pKg of about 2.5 pH units resulted from the fluorine substitution. Included in biological studies were effects on activities toward MAO. In vitro )S,)S-difluoroamphetamine was a less active inhibitor of MAO than amphetamine and )S,)S-difluorophenylethylamine was a poorer substrate for deamination than phenylethylamine. A/-Cyclopropyl-4-chlorophenylethylamine is an irreversible inhibitor of MAO. There was little difference in vivo in MAO inhibition in various tissues of the rat [72]. 

One of the earliest comparisons of thiophene to benzene in a biological system compared the vasoconstrictor activity of phenylethylamine (362 Ar = Ph) with that of 2-thienyIethyl-amine (362 Ar = 2-thienyl). It was shown to have vasopressor activity in the cat, but was only about one-tenth as potent. Phenylalanine is an essential amino acid for the growth of yeast, bacteria and mammals. It was found that /3-2-thienylalanine (363 Ar = 2-thienyl) was an antimetabolite of this essential amino acid, and numerous studies on the active L-form and simple peptides derived from it have been made. 

Rh2(55-mepy)4] was first used for cyclo-propanation. Enantioselective cyclopropana-tion is industrially important since synthetic pyrethroids, which are used as insecticides, contain substituted three-membered rings, whose configuration is crucial for their biological effect. [9] Enantioselective cyclopropa-nation has tradition. It was this reaction type which in 1966 opened up the field of enantioselective homogeneous catalysis with transition metal complexes. The copper(II) complex of the Schiff base from salicylaldehyde and optically active 1-phenylethylamine at that time reached 6% ee. [10] With optimized opti-... 

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