Synthesis of 4-alkyl- and 4-(.beta.-alkylvinyl) derivatives of primaquine as potential antimalarials

4(beta-Alkylvinyl)-6-methoxy-8-nitroquinolines (6) were prepared from 6-methoxy-8-nitroquinoline-4-carboxaldehyde (5) via a Wittig reaction. Stannous chloride reduction of 6 gave 4-(beta-alkylvinyl)-8-amino-6-methoxyquinolines (8), whereas catalytic reduction of 6 using Raney nickel catalyst gave 4-...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1979-11, Vol.22 (11), p.1363-1367
Main Authors: Carroll, F. Ivy, Berrang, Bertold D, Linn, C. Preston
Format: Article
Language:English
Subjects:
Animals
Haplorhini
Macaca mulatta
Malaria - prevention & control
Mice
Plasmodium
Plasmodium berghei
Primaquine - analogs & derivatives
Primaquine - chemical synthesis
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Summary:4(beta-Alkylvinyl)-6-methoxy-8-nitroquinolines (6) were prepared from 6-methoxy-8-nitroquinoline-4-carboxaldehyde (5) via a Wittig reaction. Stannous chloride reduction of 6 gave 4-(beta-alkylvinyl)-8-amino-6-methoxyquinolines (8), whereas catalytic reduction of 6 using Raney nickel catalyst gave 4-alkyl-8-amino-6-methoxyquinolines (7). Alkylation of 7 and 8 with 4-iodo-1-phthalimidopentane, followed by removal of the phthaloyl-protecting group with hydrazine, gave 4-alkyl and 4-(beta-alkylvinyl) derivatives of primiquine, respectively. These compounds were evaluated for antimalarial activity against P. berghei and P. berghei yoelii in mice and against P. cynomolgi in rhesus monkeys. Several of the compounds were active in the P. bergheii yoelii screen. None of the compounds showed significant activity in the other two screens.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00197a016