Synthesis and copper-dependent antimycoplasmal activity of 1-amino-3-(2-pyridyl)isoquinoline derivatives. 2. Amidines.
In our search for new compounds with antimycoplasmal activity, a series of aromatic amidines derived from 1-amino-3-(2-pyridyl)isoquinoline (1) was synthesized. In the presence of 40 microM copper the most active compounds show growth inhibition of Mycoplasma gallisepticum in the nanomolar range. These compounds are 3 times as active as tylosin, an antimycoplasmal therapeutic agent that is used in veterinary practice. In the presence of copper, amidines derived from 1 are 2-3 times more active than the corresponding amides. Furthermore it was established that for these compounds too, the presence of a 2,2'-bipyridyl moiety is a necessary prerequisite for antimycoplasmal activity. As for the amides, antimycoplasmal activity of amidines derived from 1 is dependent on the hydrophobic fragmental value of the aromatic nucleus of the amidine moiety. A quantitative structure-activity relationship established the optimal hydrophobic fragmental value of this part of the molecule to be zero.
de Zwart
M A
MA
Department of Pharmacochemistry, Vrije Universiteit, Amsterdam, The Netherlands.
van der Goot
H
H
Timmerman
H
H
D000578:Amidines / Q000138:chemical synthesis* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D009174:Mycoplasma / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000578:Amidines; D000900:Anti-Bacterial Agents; D003300:Copper