title: Cardiotonic agents. 3. A topographical model of the cardiac cAMP phosphodiesterase receptor.
abstract: Based on the pharmacophoric relationship heterocycle-phenyl-imidazole (H-P-I) and upon consideration of several potent inhibitors of cardiac cAMP phosphodiesterase, a topographical model of this receptor is proposed. The model consists of two binding sites which interact with H, two steric features, preferential rotation of P away from coplanarity with H, and a binding site for an electron-rich system (I). It is supported by molecular modeling studies and accommodates a variety of inhibitors. It also encompasses the active site of the enzyme and can distinguish cAMP from cGMP as substrates.
authors.affiliation: Berlex Laboratories, Inc., Cedar Knolls, New Jersey 07927.
authors.forename: P W
authors.initials: PW
authors.lastname: Erhardt
authors.forename: A A
authors.initials: AA
authors.lastname: Hagedorn
authors.forename: M
authors.initials: M
authors.lastname: Sabio
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D002316:Cardiotonic Agents; D003198:Computer Simulation; D008024:Ligands; D009206:Myocardium / Q000201:enzymology; D010726:Phosphodiesterase Inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D002316:Cardiotonic Agents; D008024:Ligands; D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases