The Synthesis of Potential Antiparasitic Drugs
Final rept. 1 Apr 1988-31 Mar 1990
FRANKLIN RESEARCH CENTER NORRISTOWN PA
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During the period from 1 April 1988 - 31 March 1990, we submitted to WRAIR 23 Target compounds Table I and 26 intermediates Table II. In earlier work, we prepared a series of primaquines with a methyl group at position 4 and a phenylalkoxy group at position 5. These compounds combined low toxicity with a unique dual efficacy against the blood and tissue forms at the malarial parasite. During the past two years, we have attempted to enhance this series by attaching various substituents to the phenyl portion of the 5-phenylalkoxy group Tables III - V. We have also prepared several compounds in which the terminal phenyl has been replaced by heterocycles Table VI. At the request of USAMRDC, we have prepared a third group of primaquines which are trisubstituted these compounds combine a 5-phenoxy or 5-alkoxy group with two additional substituents these compounds combine a 5-phenoxy or 5-alkoxy group with two additional substituents on the pyridine ring of the quinoline nucleus. Tables VII - X. Radical curative screening data for the new compounds are too sparse for SAR correlation but some blood schizontocidal comparisons are presented. Keywords Antiparasitic drugs, Malaria, Primaquine, SAR, 8-aminoquinolines, Blood schizontocides, Tissue schizontocides, Synthesis, RA 1, Pharmacology.