- SUBSTITUTED INDOLINE DERIVATIVES AS DENGUE VIRAL REPLICATION INHIBITORS
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The present invention relates to substituted indoline derivatives, methods to prevent or treat dengue viral infections by using said compounds and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.
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- SUBSTITUTED INDOLINE DERIVATIVES AS DENGUE VIRAL REPLICATION INHIBITORS
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The present invention concerns substituted indoline derivatives, methods to prevent or treat dengue viral infections by using said compounds and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.
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- SUBSTITUTED INDOLINE DERIVATIVES AS DENGUE VIRAL REPLICATION INHIBITORS
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The present invention concerns substituted indoline derivatives, methods to prevent or treat dengue viral infections by using said compounds and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.
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- SUBSTITUTED INDOLINE DERIVATIVES AS DENGUE VIRAL REPLICATION INHIBITORS
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The present invention concerns substituted indoline derivatives, methods to prevent or treat dengue viral infections by using said compounds and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent dengue viral infections. The present invention furthermore relates to pharmaceutical compositions or combination preparations of the compounds, to the compositions or preparations for use as a medicine, more preferably for the prevention or treatment of dengue viral infections. The invention also relates to processes for preparation of the compounds.
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- SUBSTITUTED INDOLINE DERIVATIVES AS DENGUE VIRAL REPLICATION INHIBITORS
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The present invention concerns substituted indoline compounds, methods to prevent or treat dengue viral infections by using said compounds and also relates to said compounds for use as a medicine, more preferably for use as a medicine to treat or prevent
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- A divergent SAR study allows optimization of a potent 5-HT2c inhibitor to a promising antimalarial scaffold
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From the 13-533 chemical structures published by GlaxoSmithKline in 2010, we identified 47 quality starting points for lead optimization. One of the most promising hits was the TCMDC-139046, a molecule presenting an indoline core, which is well-known for its anxiolytic properties by interacting with serotonin antagonist receptors 5-HT2. The inhibition of this target will complicate the clinical development of these compounds as antimalarials. Herein, we present the antimalarial profile of this series and our efforts to avoid interaction with this receptor, while maintaining a good antiparasitic potency. By using a double-divergent structure-activity relationship analysis, we have obtained a novel lead compound harboring an indoline core.
- Calderon, Felix,Vidal-Mas, Jaume,Burrows, Jeremy,De La Rosa, Juan Carlos,Jimenez-Diaz, Maria Belen,Mulet, Teresa,Prats, Sara,Solana, Jorge,Witty, Michael,Gamo, Francisco Javier,Fernandez, Esther
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supporting information; experimental part
p. 373 - 377
(2012/06/30)
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- Novel and selective 5-HT(2C/2B) receptor antagonists as potential anxiolytic agents: Synthesis, quantitative structure - Activity relationships, and molecular modeling of substituted 1-(3- pyridylcarbamoyl)indolines
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The synthesis, biological activity, and molecular modeling of a novel series of substituted 1-(3-pyridylcarbamoyl)indolines are reported. These compounds are isosteres of the previously published indole urea 1 (SB- 206553) and illustrate the use of aromatic disubstitution as a replacement for fused five-membered rings in the context of 5-HT(2C/2B) receptor antagonists. By targeting a region of space previously identified as sterically allowed at the 5-HT(2C) receptor but disallowed at the 5-HT(2A) receptor, we have identified a number of compounds which are the most potent and selective 5-HT(2C/2B) receptor antagonists yet reported. 46 (SB-221284) was selected on the basis of its overall biological profile for further evaluation as a novel, potential nonsedating anxiolytic agent. A CoMFA analysis of these compounds produced a model with good predictive value and in addition good qualitative agreement with both our 5-HT(2C) receptor model and our proposed binding mode for this class of ligands within that model.
- Bromidge, Steven M.,Dabbs, Steven,Davies, David T.,Duckworth, D. Malcolm,Forbes, Ian T.,Ham, Peter,Jones, Graham E.,King, Frank D.,Saunders, Damian V.,Starr, Susannah,Thewlis, Kevin M.,Wyman, Paul A.,Blaney, Frank E.,Naylor, Christopher B.,Bailey, Fiona,Blackburn, Thomas P.,Holland, Vicky,Kennett, Guy A.,Riley, Graham J.,Wood, Martyn D.
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p. 1598 - 1612
(2007/10/03)
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