142847-16-3Relevant academic research and scientific papers
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.
body text, 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.
7-(3',4'-DIALKOXYPHENYL)-[1,2,4]-TRIAZOLO[1,5-A]PYRIMIDINE COMPOUNDS, PROCESS FOR PREPARING THEREOF, AND PHARMACEUTICAL COMPOSITION FOR TREATING OR PREVENTING ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, ARTHRITIS, ATOPIC DERMATITIS, TUMOR AND DEGENERATIVE BRAIN DISEASES COMPRISING THE SAME
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, (2008/12/04)
The present invention relates to novel {7-(3',4'-dialkoxyphenyl)-[1,2,4]-triazolo[1,5-a]pyrimidine compounds or pharmaceutically acceptable salts thereof, a process for preparing the same, and pharmaceutical compositions for treating or preventing inflammatory diseases including asthma and chronic obstructive pulmonary disease, arthritis, atopic dermatitis, cancers including leukemia, and degenerative brain diseases including Alzheimer's disease, depression and memory impairment, which comprises the same as an active ingredient.
