synthetic medicinal chemistry in chagas’ disease compounds at the final stage of “hit-to-lead” phase在南美洲锥虫病化合物合成药物化学的最后阶段u201chit-to-leadu201d阶段.pdfVIP

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synthetic medicinal chemistry in chagas’ disease compounds at the final stage of “hit-to-lead” phase在南美洲锥虫病化合物合成药物化学的最后阶段u201chit-to-leadu201d阶段.pdf

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synthetic medicinal chemistry in chagas’ disease compounds at the final stage of “hit-to-lead” phase在南美洲锥虫病化合物合成药物化学的最后阶段u201chit-to-leadu201d阶段

Pharmaceuticals 2010, 3, 810-838; doi:10.3390/ph3040810 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Synthetic Medicinal Chemistry in Chagas’ Disease: Compounds at The Final Stage of “Hit-To-Lead” Phase Hugo Cerecetto 1,* and Mercedes González 2,* 1 Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay 2 Laboratorio de Química Orgánica, Instituto de Química Biológica-Facultad de Ciencias, Universidad de la República, Iguá 4225, Montevideo 11400, Uruguay * Authors to whom correspondence should be addressed; E-Mail: hcerecet@.uy (H.C.); megonzal@.uy (M.G.); Tel.: +59-82-525-0749; Fax: +59-82-525-0749. Received: 1 February 2010; in revised form: 15 March 2010 / Accepted: 19 March 2010 / Published: 25 March 2010 Abstract: Chagas’ disease, or American trypanosomosiasis, has been the most relevant illness produced by protozoa in Latin America. Synthetic medicinal chemistry efforts have provided an extensive number of chemodiverse hits at the “active-to-hit” stage. However, only a more limited number of these have been studied in vivo in models of Chagas’ disease. Herein, we survey some of the cantidates able to surpass the “hit-to-lead” stage discussing their limitations or merit to enter in clinical trials in the short term. Keywords: Chagas’ disease; “hit-to-lead”; drug-likeness 1. Introduction Despite the fact that Carlos Chagas completely described, near to a century ago [1]