- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides compounds of formula I: [INSERT FORMULA HERE] or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising such compounds and methods of using such compounds for treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease, such as malaria, caused by a Plasmodium parasite.
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Page/Page column 122
(2014/06/11)
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- Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents
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The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy)phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC50 = 190 nM and with cellular GI50 = 2100 nM, and 6-{2-[4-(2- dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC50 = 9 nM and GI50 = 220 nM.
- Niculescu-Duvaz, Dan,Niculescu-Duvaz, Ion,Suijkerbuijk, Bart M.J.M.,Ménard, Delphine,Zambon, Alfonso,Davies, Lawrence,Pons, Jean-Francois,Whittaker, Steven,Marais, Richard,Springer, Caroline J.
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p. 1284 - 1304
(2013/03/14)
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- HETEROCYCLIC BIARYL DERIVATIVE AND PDE INHIBITOR COMPRISING SAME AS ACTIVE INGREDIENT
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Novel heterocyclic biaryl derivatives were disclosed which are useful as pharmaceutical agents and which exhibit a phosphodiesterase-inhibitory action. The heterocyclic biaryl derivatives are represented by the following general formula (1): wherein the H
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Page/Page column 31
(2011/08/04)
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