Synthesis and antileishmanial activity of 6-methoxy-4-methyl-N-[6-(substituted-1-piperazinyl)hexyl]-8-quinolinamines and related compounds.
The 8-quinolinamine, 4-[6-[6-methoxy-4-methyl-8-quinolinyl)amino]hexyl]-1-piperazineethanol (1b), has been shown to be highly effective against Leishmania donovani infections in hamsters. In an effort to obtain a more potent, less toxic 8-quinolinamine, a series of analogues (2) was prepared that examined particularly the structural requirements of the terminal piperazine moiety. Of the substituted piperazines and alternative heterocycles prepared, as well as those quinoline analogues with ring insertion of a methyl group in the 2-position or an aryloxy substituent in the 5-position, an increase in potency was achieved only with the 2-hydroxypropyl analogue (2f).
D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis*; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D007891:Leishmania / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy*; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000871:Anthelmintics; D007202:Indicators and Reagents; D010879:Piperazines