Carboxylic acids and skeletal muscle chloride channel conductance: effects on the biological activity induced by the introduction of an aryloxyalkyl group alpha to the carboxylic function of 4-chloro-phenoxyacetic acid.
2-(4-Chloro-phenoxy)propanoic and 2-(4-chloro-phenoxy)butanoic acids are compounds known to block chloride membrane conductance in rat striated muscle by interaction with a specific receptor. In the present study, a series of chiral analogues has been prepared and tested to evaluate the influence of a second aryloxy moiety introduced in the side-chain at a variable distance from the stereogenic centre. The results show that this chemical modification is detrimental for biological activity which, however, is increased by lengthening the alkyl chain up to three methylenic groups, then decreases to remain constant in the next analogues of the series. A possible explanation for this is proposed on the basis of steric effects and/or different approach of the molecules to the receptor.
Carbonara
G
G
Dipartimento Farmaco-Chimico, Università di Bari, Italy.
Fracchiolla
G
G
Loiodice
F
F
Tortorella
P
P
Conte-Camerino
D
D
De Luca
A
A
Liantonio
A
A
D015084:2,4-Dichlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000737:chemistry*; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects*; D002995:Clofibric Acid / Q000031:analogs & derivatives*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D002264:Carboxylic Acids; D018118:Chloride Channels; D015084:2,4-Dichlorophenoxyacetic Acid; C007017:4-chlorophenoxyacetic acid; D002995:Clofibric Acid