ChemInform Abstract: Synthesis of 4,4-Bis(2-methylphenyl)-3-butenyl (and butyl) Analogues of 4-Phenyl-1,4,- and 6-Phenyl-1,6-dihydropyridine-3-carboxylic Acids and Their Evaluation as Neuronal GABA-Uptake Inhibitors.

✍ Scribed by N. IQBAL; Z.-Y. WEI; G. B. BAKER; E. E. KNAUS

• Publisher: John Wiley and Sons
• Year: 2010
• Weight: 37 KB
• Volume: 28
• Category: Article
• ISSN: 0931-7597
• DOI: 10.1002/chin.199752163

✦ Synopsis

Synthesis of 4,4-Bis(2-methylphenyl)-3-butenyl (and butyl) Analogues of 4-Phenyl-1,4,-and 6-Phenyl-1,6-dihydropyridine-3-carboxylic Acids and Their Evaluation as Neuronal GABA-Uptake Inhibitors. -All attempts to hydrolyze the esters (VIII) and (IX) to a carboxyl group result in decomposition products. In contrast, the corresponding cyanoethyl esters (XII) and (XIII) are readily converted to the corresponding carboxyl analogues as demonstrated for (XIV). Structure-activity correlations are discussed in terms of biological evaluations of these compounds as GABA-uptake inhibitors compared to nipecotic acid (XV) and guvacine (XVI). In general, 1,6-dihydropyridyl compounds are more potent than corresponding 1,4-dihydropyridyl isomers and compounds with a carboxyl group show higher potency than those with an ester group. However, inhibition (21-44%) is remarkably decreased compared to (XV) (87% inhibition). -(IQBAL, N.