Nicotinamide ethers: novel inhibitors of calcium-independent phosphodiesterase and [3H]rolipram binding

• Published in: Journal of medicinal chemistry Vol. 34; no. 1; pp. 86 - 89
• Main Authors: Vinick, Fredric J, Saccomano, Nicholas A, Koe, B. Kenneth, Nielsen, Jann A, Williams, Ian H, Thadeio, Peter F, Jung, Stanley, Meltz, Morgan, Johnson, Jonathan, Lebel, Lorraine A, Russo, Lorena L, Helweg, David
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01-01-1991
• Subjects: Animals; Binding Sites; Body Temperature Regulation - drug effects; Brain - metabolism; Chemistry; Ethers; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Indicators and Reagents; Magnetic Resonance Spectroscopy; Mass Spectrometry; Mice; Molecular Structure; Niacinamide - analogs & derivatives; Niacinamide - chemical synthesis; Niacinamide - pharmacology; Organic chemistry; Phosphodiesterase Inhibitors - chemical synthesis; Preparations and properties; Protein Binding; Pyrrolidinones - metabolism; Pyrrolidinones - pharmacology; Rats; Reserpine - pharmacology; Rolipram; Structure-Activity Relationship; Ether; Nitrogen heterocycle; Phosphodiesterase II; Enzyme inhibitor; Carboxamide; Phosphodiesterase I; Biological activity
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00105a015

The synthesis and biological properties of a series of nicotinamide ethers are described. These compounds, structurally novel calcium-independent phosphodiesterase inhibitors, also inhibit the binding of [3H]rolipram to rat brain membranes and reverse reserpine-induced hypothermia in the mouse. Several compounds exhibited potent in vivo activity comparable to the standard agent, rolipram.