| Literature DB >> 9526558 |
S B Christensen1, A Guider, C J Forster, J G Gleason, P E Bender, J M Karpinski, W E DeWolf, M S Barnette, D C Underwood, D E Griswold, L B Cieslinski, M Burman, S Bochnowicz, R R Osborn, C D Manning, M Grous, L M Hillegas, J O Bartus, M D Ryan, D S Eggleston, R C Haltiwanger, T J Torphy.
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.Entities:
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Year: 1998 PMID： 9526558 DOI： 10.1021/jm970090r
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446