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