title: Design and synthesis of the first potent, selective, and cell penetrating adenosine 5'-monophosphate deaminase inhibitors.
abstract: A major milestone in purine metabolism research has been achieved with the discovery of these potent and selective AMPDA inhibitors. These inhibitors of AMPDA are based on carboxypentyl substitution on N-3 of the coformycin aglycon. They are simpler than coformycin ribose 5'-monophosphate, more stable, selective against other AMP binding enzymes as well as ADA and have good cell penetration and good oral bioavailability. These compounds and their more potent analogs are the first compounds with suitable characteristics to allow a definitive analysis of the role of AMPDA in cellular metabolism and AMPDA as a therapeutic target.
authors.affiliation: Metabasis Therapeutics Inc., San Diego, California 92121, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Bookser
authors.forename: S R
authors.initials: SR
authors.lastname: Kasibhatla
authors.forename: J R
authors.initials: JR
authors.lastname: Appleman
authors.forename: M D
authors.initials: MD
authors.lastname: Erion
mesh_terms: D000659:AMP Deaminase / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D001682:Biological Availability; D003070:Coformycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D003070:Coformycin; D000659:AMP Deaminase