Synthesis and Evaluation of 1,1′‐Hydrocarbylenebis(indazol‐3‐ols) as Potential Antimalarial Drugs |
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| Authors: | Miriam Martins Alho Dr. Rory N. García‐Sánchez Juan José Nogal‐Ruiz Dr. José Antonio Escario Dr. Alicia Gómez‐Barrio Dr. Antonio R. Martínez‐Fernández Dr. Vicente J. Arán Dr. |
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| Affiliation: | 1. CIHIDECAR (CONICET), Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires (Argentina);2. Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, 28040 Madrid (Spain), Fax: (+34)?91‐394‐1815;3. Instituto de Química Médica (IQM), CSIC c/Juan de la Cierva 3, 28006 Madrid (Spain), Fax: (+34)?91‐564‐4853 |
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| Abstract: | Bis(indazol‐3‐ol) derivatives ( 5 , 30–38 ) were prepared by alkylation of 3‐alkoxyindazoles with α,ω‐dibromides, followed by removal of the O‐protecting groups. These compounds were subsequently evaluated as inhibitors of biocrystallization of ferriprotoporphyrin IX (heme) to hemozoin, a Plasmodium detoxification specific process. Most bis(5‐nitroindazol‐3‐ols) were good inhibitors, however, a denitro analogue ( 38 ), the intermediate bis(3‐alkoxyindazoles) ( 15 – 29 ) as well as bis(indazolin‐3‐ones) ( 39 – 42 ) were not active, showing the importance of the NO2 and OH groups in the inhibition process. |
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| Keywords: | alkylation antimalarial agents drug design inhibitors nitrogen heterocycles |
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