Quaternary substituted PDE4 inhibitors I: The synthesis and in vitro evaluation of a novel series of oxindoles

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 2; pp. 175 - 178
• Main Authors: Hulme, Christopher, Poli, Gregory B., Fu-Chih Huang, Souness, John E., Djuric, Stevan W.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 20.01.1998; Elsevier
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Biological and medical sciences; Cyclic Nucleotide Phosphodiesterases, Type 4; Immunomodulators; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Medical sciences; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - chemical synthesis; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - pharmacology; Pyridines - chemistry; Pyridines - pharmacology; Structure-Activity Relationship; 3',5'-Cyclic-nucleotide phosphodiesterase; Enzyme; Nitrogen heterocycle; Lactam; Enzyme inhibitor; Esterases; Phosphoric diester hydrolases; Organic carbamate; Pyridine derivatives; Position isomer; Structure activity relation; Bicyclic compound; Hydrolases; Benzenic compound; Aromatic compound; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(97)10206-2

The following letter presents the synthesis and in vitro evaluation of a novel quaternary substituted series of phosphodiesterase type (IV) (PDE4) inhibitors. The compounds represent conformationally constrained analogues of the Celltech PDE IV inhibitor, CDP 840. Examples with sub-micromolar IC 50's for PDE4 inhibition are reported. The synthesis and in vitro evaluation of a novel series of phosphodiesterase type (IV) (PDE4) inhibitors is presented. The compounds represent conformationally constrained analogues of the Celltech PDE4 inhibitor, CDP840 and are represented by the general structure 1.