1,4-Cyclohexanecarboxylates: potent and selective inhibitors of phosophodiesterase 4 for the treatment of asthma |
| |
Authors: | SB Christensen A Guider CJ Forster JG Gleason PE Bender JM Karpinski WE DeWolf MS Barnette DC Underwood DE Griswold LB Cieslinski M Burman S Bochnowicz RR Osborn CD Manning M Grous LM Hillegas JO Bartus MD Ryan DS Eggleston RC Haltiwanger TJ Torphy |
| |
Affiliation: | SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. |
| |
Abstract: | Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity 3H]rolipram-binding sites in the central nervous system. Use of this strategy led ultimately to the identification of cis-4-cyano-4-3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxyl ic acid (1, SB 207499, Ariflo), a potent second-generation inhibitor of PDE4 with a decreased potential for side effects versus the archetypic first generation inhibitor, (R)-rolipram. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|