Abstract
A novel series of 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines was synthesized and their TbetaR-1 inhibitory, p38 MAPK inhibitory, and TbetaR-1-dependent cellular activity were evaluated. Compound 5a was found to be a highly potent in the enzyme assay and TbetaR-1-dependent cellular assays. In addition, dimer (4g), with a urea linker, shows a similar enzyme and cellular activity despite a bulky substitution.
MeSH terms
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Activin Receptors, Type I / antagonists & inhibitors*
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Cells, Cultured
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Dimerization
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Humans
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Inhibitory Concentration 50
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Protein Serine-Threonine Kinases
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Protein Structure, Tertiary
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Pyrazoles / chemical synthesis
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Pyrazoles / pharmacology
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Pyrroles / chemical synthesis
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Pyrroles / pharmacology
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Quinolines / chemical synthesis
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Quinolines / pharmacology
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Transforming Growth Factor beta / antagonists & inhibitors*
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Structure-Activity Relationship
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Urea / chemistry
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p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Pyrazoles
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Pyrroles
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Quinolines
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Receptors, Transforming Growth Factor beta
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Urea
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Protein Serine-Threonine Kinases
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p38 Mitogen-Activated Protein Kinases
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I