Carboxylic acids and skeletal muscle chloride channel conductance: effects on the biological activity induced by the introduction of methyl groups on the aromatic ring of chiral alpha-(4-chloro-phenoxy)alkanoic acids.
One or two methyl groups have been introduced on the aromatic ring of two chiral clofibric acid analogs, 2-(4-chloro-phenoxy)propanoic and 2-(4-chloro-phenoxy)butanoic acids. The biological activity of the derivatives obtained (3-6) has been evaluated on the skeletal muscle chloride conductance (gCl). The results confirm the hypothesis of two different sites modulating chloride channel function, an excitatory site that increases channel activity and an inhibitory site that produces a channel block. In fact, this chemical modification strongly reduces the blocking activity of the (R)- and (S)-enantiomers in comparison with the parent compounds, but does not markedly affect the ability of the (R)-enantiomers to increase chloride channel conductance.
Ferorelli
S
S
Dipartimento Farmaco-Chimico, Università di Bari, via Orabona 4, 70126 Bari, Italy.
Loiodice
F
F
Tortorella
V
V
Conte-Camerino
D
D
De Luca
A M
AM
D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D002942:Circular Dichroism; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000473:Alkanes; D002264:Carboxylic Acids; D018118:Chloride Channels