Naphthyridinone Antimalarial Prophylactics.

摘要

4-Amino-1,5-naphthyridines have been envisioned as structural contours of both 4-amino and 8-aminoquinoline antimalarial agents. These derivatives have, however, only been effective against the asexual erythrocytic stages of the parasite. None of the reported variations show the prophylactic behavior characteristic of 8-aminoquinoline drugs. Recently oxidation of the 1,5-naphthyridine nucleus to the 1,5-naphthyridin-2-one resulted in drugs responsive to the Schmidt prophylactic antimalarial screen. The work detailed herein was an attempt to amplify earlier work through (a) further alterations of the naphthyridin-2-one nucleus and (b) attachment of diamino sidechains noted to be significant to the prophylactic agents pamaquine, pentaquine, primaquine, and quinocide. The latter two types of sidechains received particular emphasis. A total of 18 target drugs substituted in the 1,5-naphthyridin-2-one C-4 position by diaminoalkane functions was synthesized during this contract. No biological data is yet available.