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Synthesis and SAR Studies of 1H-Pyrrolo[2,3-b]pyridine-2-carboxamides as Phosphodiesterase 4B (PDE4B) Inhibitors.

ABSTRACT: Herein we report the synthesis, SAR, and biological evaluation of a series of 1H-pyrrolo[2,3-b]pyridine-2-carboxamide derivatives as selective and potent PDE4B inhibitors. Compound 11h is a PDE4B preferring inhibitor and exhibited acceptable in vitro ADME and significantly inhibited TNF-α release from macrophages exposed to pro-inflammatory stimuli (i.e., lipopolysaccharide and the synthetic bacterial lipopeptide Pam3Cys). In addition, 11h was selective against a panel of CNS receptors and represents an excellent lead for further optimization and preclinical testing in the setting of CNS diseases.

SUBMITTER: Vadukoot AK

PROVIDER: S-EPMC7549101 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice.

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| S-EPMC10463376 | biostudies-literature

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