Pharmacokinetics, biodistribution and toxicology following intravenous and oral administration of DSM-RX78 and EFB-1, two new 2-(2-fluorobenzamido)benzoate-based PDE4 inhibitors, to rats.

Objectives: The aim of this study was to determine the pharmacokinetic profile, biodistribution and toxicity of ethyl 2-(2-fluorobenzamido)benzoate (EFB-1) and methyl 2-(2-fluorobenzamido)benzoate (DSM-RX 78), two phosphodiesterase IV inhibitors, which potently attenuate haemorrhagic shock-induced lung injury in rat.

Methods: Quantification of DSM-RX78, EFB-1 and 2-(2-fluorobenzamido)benzoate (SMP-3) in plasma was carried out by HPLC. Furthermore, the pharmacokinetics and biodistribution of intravenously (1.

Anthranilic acid-based inhibitors of phosphodiesterase: design, synthesis, and bioactive evaluation.

Our previous studies identified two 2-benzoylaminobenzoate derivatives 1, which potently inhibited superoxide (O(2)˙(-)) generation induced by formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) in human neutrophils. In an attempt to improve their activities, a series of anthranilic acid derivatives were synthesized and their anti-inflammatory effects and underlying mechanisms were investigated in human neutrophils. Of these, compounds 17, 18, 46, 49, and 50 showed the most potent inhibitory effect on FMLP-induced release of O(2)˙(-) in human neutrophils with IC(50) values of 0.