Choleretic activity of 3-[ring substituted benzotriazol-1(2)-yl]alkanoic and alkenoic acids.
In order to investigate the influence of structural modifications on the high choleretic activity of 3-(benzotriazol-1-yl)butanoic acid, a set of new benzotriazolyl alkanoic and alkenoic acids was prepared and, together with some other acids previously described, tested in rats by i.v. administration at the dose of 0.5 mmol/kg. Most of the tested compounds exhibited a good choleretic activity comparable with or higher than that of the model acid and of dehydrocholic acid (+56% mean increase of bile volume during 4 hours). Influence of nature and position of substituents was shown in some cases: a moderate decrease of activity was observed for methoxy derivatives and for the introduction of a methyl group in position 6, while a trifluoromethyl group in the same position enhanced the activity (10). Activity was maintained after the introduction of unsaturation in the chain (17,18), but was completely suppressed when unsaturation was associated with a shortening of the alkenoic chain (16). Moving the butanoic chain from position 1 to position 2 in the case of the nitroderivative (15) produced a striking increase of activity (from +42 to +118 mean variation of bile volume during 4 hours), while the same change in the unsubstituted acid 1 abolished the activity.
Paglietti
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Istituto di Chimica Farmaceutica e Tossicologica, Università di Sassari.
Sanna
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P
Carta
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A
Sparatore
F
F
Vazzana
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I
Peana
A
A
Satta
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M
D000818:Animals; D002756:Cholagogues and Choleretics / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D002756:Cholagogues and Choleretics; D014230:Triazoles; C012771:benzotriazole