19743-75-0Relevant academic research and scientific papers
Pyrazolopyridines as a novel structural class of potent and selective PDE4 inhibitors
Hamblin, J. Nicole,Angell, Tony D.R.,Ballantine, Stuart P.,Cook, Caroline M.,Cooper, Anthony W.J.,Dawson, John,Delves, Christopher J.,Jones, Paul S.,Lindvall, Mika,Lucas, Fiona S.,Mitchell, Charlotte J.,Neu, Margarete Y.,Ranshaw, Lisa E.,Solanke, Yemisi E.,Somers, Don O.,Wiseman, Joanne O.
scheme or table, p. 4237 - 4241 (2009/04/07)
Optimisation of a high-throughput screening hit resulted in the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective inhibitors of Phosphodiesterase 4 (PDE4). Herein, we describe early SAR studies around this novel template highlighting preferred substituents and rationalization of SAR through X-ray crystal structures of analogues bound to the PDE4 active site. Pyrazolopyridine 20a was found to be a potent and selective PDE4 inhibitor which also inhibits LPS induced TNF-α production from isolated human peripheral blood mononuclear cells and has an encouraging rat PK profile suitable for oral dosing.
Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors
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Page/Page column 22, (2010/01/31)
Compounds of the formula which are useful in disease conditions mediated by TNF-α, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.
Synthesis and SAR of bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors
Zask,Gu,Albright,Du,Hogan,Levin,Chen,Killar,Sung,DiJoseph,Sharr,Roth,Skala,Jin,Cowling,Mohler,Barone,Black,March,Skotnicki
, p. 1487 - 1490 (2007/10/03)
Potent and selective bicyclic heteroaryl hydroxamic acid MMP and TACE inhibitors were synthesized by a novel convergent route. Selectivity and efficacy versus MMPs and TACE could be controlled by appropriate substitution on the scaffolds and by variation of the P1′ group. Select compounds were found to be effective in in vivo models of arthritis.
