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

C Hulme; G B Poli; F C Huang; J E Souness; S W Djuric

doi:10.1016/s0960-894x(97)10206-2

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

Bioorg Med Chem Lett. 1998 Jan 20;8(2):175-8. doi: 10.1016/s0960-894x(97)10206-2.

Authors

C Hulme¹, G B Poli, F C Huang, J E Souness, S W Djuric

Affiliation

¹ Rhône-Poulenc Rorer Central Research, Collegeville, PA 19426, USA.

PMID: 9871649
DOI: 10.1016/s0960-894x(97)10206-2

Abstract

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 IC50's for PDE4 inhibition are reported.

MeSH terms

3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
Cyclic Nucleotide Phosphodiesterases, Type 4
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology
Phosphodiesterase Inhibitors / chemical synthesis*
Phosphodiesterase Inhibitors / chemistry
Phosphodiesterase Inhibitors / pharmacology
Pyridines / chemistry*
Pyridines / pharmacology
Structure-Activity Relationship

Substances

Indoles
Phosphodiesterase Inhibitors
Pyridines
CDP 840
3',5'-Cyclic-AMP Phosphodiesterases
Cyclic Nucleotide Phosphodiesterases, Type 4