Synthesis and SAR Studies of 1<i>H</i>‑Pyrrolo[2,3‑<i>b</i>]pyridine-2-carboxamides as Phosphodiesterase 4B (PDE4B) Inhibitors Anish K. Vadukoot Swagat Sharma Christopher D. Aretz Sushil Kumar Nagsen Gautam Yazen Alnouti Amy L. Aldrich Cortney E. Heim Tammy Kielian Corey R. Hopkins 10.1021/acsmedchemlett.9b00369.s001 https://acs.figshare.com/articles/journal_contribution/Synthesis_and_SAR_Studies_of_1_i_H_i_Pyrrolo_2_3_i_b_i_pyridine-2-carboxamides_as_Phosphodiesterase_4B_PDE4B_Inhibitors/11794086 Herein we report the synthesis, SAR, and biological evaluation of a series of 1<i>H</i>-pyrrolo­[2,3-<i>b</i>]­pyridine-2-carboxamide derivatives as selective and potent PDE4B inhibitors. Compound <b>11h</b> is a PDE4B preferring inhibitor and exhibited acceptable <i>in vitro</i> 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, <b>11h</b> 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. 2020-02-03 16:24:51 PDE 4B inhibitors PDE 4B Inhibitors Herein PDE 4B Compound 11 h pro-inflammatory stimuli lipopeptide Pam 3Cys CNS receptors pyridine -2-carboxamides CNS diseases SAR Studies 1 H TNF -α release ADME Phosphodiesterase 4 B 11 h