ABSTRACT
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 2-substituted 8-methoxyquinolines is described. The 2-trifluoromethyl compound was found to be a potent inhibitor of phosphodiesterase type 4 (PDE4).
Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Phosphodiesterase Inhibitors/chemical synthesis , Phosphodiesterase Inhibitors/pharmacology , Quinolines/chemical synthesis , Quinolines/pharmacology , Animals , Area Under Curve , Cyclic Nucleotide Phosphodiesterases, Type 4 , Guinea Pigs , Phosphodiesterase Inhibitors/pharmacokinetics , Quinolines/pharmacokinetics , Vomiting/chemically inducedABSTRACT
The syntheses and pharmacological profiles of some 2-trifluoromethyl-8-methoxyquinoline-5-carboxamides are described. SCH351591 is a potent selective inhibitor of phosphodiesterase type 4 (PDE4).
Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/antagonists & inhibitors , Cyclic N-Oxides/chemical synthesis , Cyclic N-Oxides/pharmacology , Phosphodiesterase Inhibitors/chemical synthesis , Phosphodiesterase Inhibitors/pharmacology , Quinolines/chemical synthesis , Quinolines/pharmacology , Animals , Area Under Curve , Cyclic N-Oxides/pharmacokinetics , Cyclic Nucleotide Phosphodiesterases, Type 4 , Guinea Pigs , Phosphodiesterase Inhibitors/pharmacokinetics , Quinolines/pharmacokineticsABSTRACT
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).