- Optimization of Physicochemical Properties for 4-Anilinoquinoline Inhibitors of Plasmodium falciparum Proliferation
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We recently reported the medicinal chemistry reoptimization of a known human tyrosine kinase inhibitor, lapatinib, against a variety of parasites responsible for numerous tropical diseases, including human African trypanosomiasis (Trypanosoma brucei), Chagas disease (T. cruzi), Leishmaniasis (Leishmania spp.), and malaria (Plasmodium falciparum). Herein, we report our continuing efforts to optimize this series against P. falciparum. Through the design of a library of compounds focused on reducing the lipophilicity and molecular weight, followed by an SAR exploration, we have identified NEU-1953 (40). This compound is a potent inhibitor of P. falciparum with an improved ADME profile over the previously reported compound, NEU-961 (3).
- Mehta, Naimee,Ferrins, Lori,Leed, Susan E.,Sciotti, Richard J.,Pollastri, Michael P.
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p. 577 - 591
(2018/04/19)
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- HYDROXYLAMINE COMPOUNDS AND METHODS OF THEIR USE
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The present disclosure provides compounds that include hydroxylamines of formula (I) or (II), pharmaceutical compositions, and methods for their use. The methods utilize hydroxylamine compounds and/or their pharmaceutical compositions for the treatment of angiogenesis, hepatitis, complement-mediated pathologies, drusen-mediated pathologies, macular degeneration and certain other ophthalmic conditions, inflammation, arthritis, and related diseases and for the inhibition of complement activation.
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Page/Page column 87
(2008/12/08)
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- Drug Resistance Reversal In Neoplastic Disease
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The present invention is directed to compounds, compositions, and methods for halting or reversing the effects of chemoresistance in neoplastic diseases. In particular the use of hydroxylamines is described.
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Page/Page column 39
(2008/12/08)
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- Novel methods and compounds employed therein
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Preparation of an optically active alkamine in the sinister configuration, or a derivative of said alkamine, which is reacted with an 3-X-4-chloro(or RO-- where R is hydrogen or an alkali metal)-1,2,5-thiadiazole to prepare S-3-X-4-(3-substituted amino-2-hydroxypropoxy)-1,2,5-thiadiazole beta adrenergic blocking agents. Novel 3-morpholino-4-chloro(or RO--)-1,2,5-thiadiazoles and their preparation also are described.
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