Synthesis and binding properties to GABA receptors of 3-hydroxypyridinyl- and 3-hydroxypiperidinyl-analogues of baclofen.
The synthesis of 3-(3-hydroxy-2-pyridinyl)propanoic acid, 3-(3-hydroxy-2-pyridinyl)-4-aminobutanoic acid, their corresponding piperidine compounds, and of some cyclized derivatives is described. In in vitro assays none of the new compounds shows any noteworthy affinity for GABAA or GABAB receptors; only (R,S)-3-(3-hydroxy-2-pyridinyl)-4-aminobutanoic acid and its lactam inhibited in some degree [3H]GABA binding, at 10(-4) M concentration, with low specificity as regards the two receptors.
Desideri
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Dipartimento di Studi farmaceutici, Università La Sapienza di Roma, Roma, Italia.
Galli
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Sestili
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Stein
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ML
D000613:Aminobutyrates / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D001418:Baclofen / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000378:metabolism; D011422:Propionates / Q000138:chemical synthesis* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*
D000613:Aminobutyrates; D010880:Piperidines; D011422:Propionates; D011725:Pyridines; D011963:Receptors, GABA-A; D001418:Baclofen