ml9b00369_si_001.pdf (641.69 kB)
Synthesis and SAR Studies of 1H‑Pyrrolo[2,3‑b]pyridine-2-carboxamides as Phosphodiesterase 4B (PDE4B) Inhibitors
journal contribution
posted on 2020-02-03, 16:24 authored by Anish
K. Vadukoot, Swagat Sharma, Christopher D. Aretz, Sushil Kumar, Nagsen Gautam, Yazen Alnouti, Amy L. Aldrich, Cortney E. Heim, Tammy Kielian, Corey R. HopkinsHerein 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.