Novel Cyclic Compounds as Potent Phosphodiesterase 4 Inhibitors
Journal of Medicinal Chemistry1998Vol. 41(22), pp. 4216–4223
Citations Over Time
Wei He, Fu‐Chih Huang, Barbara Hanney, John E. Souness, Bruce E. Miller, Guyan Liang, Jon Mason, Stevan W. Djurić
Abstract
The synthesis and biological activity of a novel series of 2, 2-disubstituted indan-1,3-dione-based PDE4 inhibitors are described. This structurally unique class of PDE4 inhibitors is markedly different from the known PDE4 inhibitors such as RP 73401 (2) and CDP 840 (3). Structure-activity relationship (SAR) studies led to the identification of inhibitors with nanomolar potency and oral activity in a murine endotoxemia model for TNF-alpha inhibition. Unlike other classical PDE4 inhibitors, several analogues were found to be nonemetic in a canine emesis model at intravenous doses of up to 3 mg/kg.
Related Papers
- → Design, synthesis and biological activity of β-carboline-based type-5 phosphodiesterase inhibitors(2003)50 cited
- → Quinazolines: Combined type 3 and 4 phosphodiesterase inhibitors(1998)23 cited
- → Quantitative Structure-Activity Relationships of 5-Lipoxygenase Inhibitors. Inhibitory Potency of Pyridazinone Analogues(1994)13 cited
- → Synthesis and biological activity of substance P C-terminal hexapeptide analogues: structure-activity studies(1986)23 cited
- Structure-activity relationship of quinolone antibacterial agents: the effects of C-2 substitution.(1990)