ABSTRACT
We describe a novel series of imidazopyridine substituted phenylalanines which are potent VLA-4 antagonists. A wide variety of substituents are tolerated as replacements for the pendant 3-pyridyl ring. A clear structure-activity relationship was identified around the substitution of the 3-amino-cyclobut-2-enone portion of the molecule.
Subject(s)
Chemistry, Pharmaceutical/methods , Integrin alpha4beta1/antagonists & inhibitors , Phenylalanine/chemistry , Pyridines/chemistry , Animals , Drug Design , Humans , Inhibitory Concentration 50 , Integrin alpha4beta1/blood , Mice , Models, Chemical , Molecular Conformation , Protein Binding , Rats , Structure-Activity RelationshipABSTRACT
A series of bicyclic heteroaryl ring systems was considered as a replacement for the 3-cyclopentyloxy-4-methoxyphenyl moiety in rolipram resulting in the discovery of 8-methoxyquinoline-5-carboxamides as potent inhibitors of phosphodiesterase type 4 (PDE4).
Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Amides/therapeutic use , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Phosphodiesterase Inhibitors/therapeutic use , Amides/pharmacology , Anti-Asthmatic Agents/pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 4 , Humans , Phosphodiesterase Inhibitors/pharmacologyABSTRACT
The synthesis and pharmacological profile of a novel series of 7-methoxy-furo[2,3-c]pyridine-4-carboxamides is described. Some of these compounds were found to be potent inhibitors of phosphodiesterase type 4 (PDE4).