784189-99-7Relevant academic research and scientific papers
PHOSPHODIESTERASE INHIBITORS
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Page/Page column 58-59, (2009/09/04)
The invention relates to compounds of formula I useful for inhibiting phosphodiesterase-4
Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors
Skoumbourdis, Amanda P.,LeClair, Christopher A.,Stefan, Eduard,Turjanski, Adrian G.,Maguire, William,Titus, Steven A.,Huang, Ruili,Auld, Douglas S.,Inglese, James,Austin, Christopher P.,Michnick, Stephen W.,Xia, Menghang,Thomas, Craig J.
supporting information; experimental part, p. 3686 - 3692 (2010/03/24)
An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively.
PYRAZOLE DERIVATIVES AS PHOSPHODIESTERASE 4 INHIBITORS
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Page 103, (2008/06/13)
Selective PDE4 inhibition is achieved by aryl and heteroaryl pyrazole compounds. The compounds exhibit improved PDE4 inhibition as compared to compounds such as rolipram and show selectivity with regard to inhibition of other classes of PDEs.
