Stereospecific synthesis of new 4-amino-1,2,3-cyclohexanetricarboxylic acids and 4-amino-1,3-cyclohexanedicarboxylic acids.

Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
CHEMICAL & PHARMACEUTICAL BULLETIN (Impact Factor: 1.56). 02/2005; 53(1):81-5.
Source: PubMed

ABSTRACT Diels-Alder adducts of 1,2-dihydropyridine with maleic and acrylic acid derivatives were stereospecifically converted by way of RuO4 oxidation into new 4-amino-1,2,3-cyclohexanetricarboxylic acids and 4-amino-1,3-cyclohexanedicarboxylic acids.

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    ABSTRACT: 1 Pyramidal cells in rat hippocampus were used to study the molecular dimensions of a receptor for inhibitory amino acids in the central nervous system. The inhibitory potencies of gamma-aminobutyrate (GABA), beta-alanine and glycine were compared by standard microiontophoretic techniques. Subsequently, rigid cyclopentane and cyclohexane amino acid analogues were applied by iontophoresis and their relative efficacies were compared with those of the naturally occurring amino acids.2 GABA was the most effective of the small aliphatic amino acids in producing inhibition of the firing of hippocampal pyramidal neurones. beta-Alanine was less effective and glycine was the least effective. GABA-induced inhibition was antagonized by concurrent iontophoresis of picrotoxin or bicuculline, whereas strychnine did not antagonize GABA inhibition.3 The ability of the series of substituted aminocyclopentane and aminocyclohexane carboxylic acids to produce inhibition of pyramidal cells was a direct function of the separation of amino and carboxylic acid groups. In both series of the cyclic amino acids the most potent inhibition was demonstrated when the spatial separation was similar to that of the extended GABA molecule (4.74 A). Additionally, the inhibition of hippocampal pyramidal cells by (+/--cis-3-amino-cyclopentanecarboxylic acid, like that produced by GABA, could be blocked by simultaneous application of picrotoxin or bicuculline, but not by strychnine.4 The present results suggest that the physiologically active conformation of GABA is the fully extended molecule, and additionally indicate that one dimension of the postsynaptic receptor site is within the range of 4.2 to 4.8 ångströms.
    British Journal of Pharmacology 07/1975; 54(2):181-8. · 5.07 Impact Factor