Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 2: metabolism-directed optimization studies towards orally bioavailable derivatives

Bioorg Med Chem Lett. 2004 Sep 20;14(18):4615-21. doi: 10.1016/j.bmcl.2004.07.009.

Abstract

The synthesis and optimization of pharmacokinetic parameters of structurally novel small PDE7 inhibitors is discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • Administration, Oral
  • Animals
  • Biological Availability
  • Cyclic Nucleotide Phosphodiesterases, Type 7
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Phosphodiesterase Inhibitors / chemical synthesis
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacokinetics*
  • Rats
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thiadiazoles / chemical synthesis
  • Thiadiazoles / chemistry
  • Thiadiazoles / pharmacokinetics*

Substances

  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Thiadiazoles
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 7