Synthesis and SAR Studies of 1 H-Pyrrolo[2,3- b]pyridine-2-carboxamides as Phosphodiesterase 4B (PDE4B) Inhibitors
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.
Vadukoot, Anish K.,Sharma, Swagat,Aretz, Christopher D.,Kumar, Sushil,Gautam, Nagsen,Alnouti, Yazen,Aldrich, Amy L.,Heim, Cortney E.,Kielian, Tammy,Hopkins, Corey R.
The present invention is directed to compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein the substituents are as defined herein.
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Paragraph 0235; 0236; 0237
(2014/09/03)
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