Structurally diverse 5-substituted pyrimidine nucleosides as inhibitors of Leishmania donovani promastigotes in vitro

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 19; pp. 5047 - 5051
• Main Authors: Torrence, Paul F., Fan, Xuesen, Zhang, Xinying, Loiseau, Philippe M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-10-2006; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - pharmacology; Biological and medical sciences; Chromene; Cyanovinyl; Inhibitory Concentration 50; Leishmania donovani; Leishmania donovani - drug effects; Medical sciences; Orthopoxvirus; Pharmacology. Drug treatments; Pyrazolone; Pyrimidine Nucleosides - chemical synthesis; Pyrimidine Nucleosides - pharmacology; Structure-Activity Relationship; Cyanovinyl; Pyrazolone; Orthopoxvirus; Chromene; Kinetoplastida; Protozoa; Chordopoxvirinae; Nitrile; Leishmania donovani; Deoxyribonucleoside; In vitro; Biological activity; Virus; Antiprotozoal agent; Poxviridae; Pyrazole derivatives; Parasiticide; Nucleoside; Inhibitor; Chemical synthesis; Pyrimidine nucleoside; Promastigote
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.07.042

A series of 5-substituted pyrimidine nucleosides with R substituents ranging from formyl, to dicyanovinyl, to substituted chromenes, and including a pyrazolone, were all potent inhibitors of
Leishmania donovani promastigotes.
The following structurally diverse 5-substituted-2′-deoxyuridine nucleosides displayed potent in vitro antileishmanial activity: 5-formyl, 5-(2,2,-dicyanovinyl)-, 5-(2-cyano-2-ethoxycarbonylvinyl), 5-(2-cyano-2-methoxycarbonylvinyl)-, 5-(2-amino-3-cyano-5-oxo-5,6,7,8-tetrahydro-4
H-chromen-4-yl)- and related congeners, and the 5-(3-methyl-5-oxo-1-phenyl-4,5-dihydro-4
H-pyrazol-4-ylidene) group.