- Discovery of Potent and Selective RSK Inhibitors as Biological Probes
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While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell functions, the full understanding of this kinase family has been restricted by the lack of highly selective inhibitors. A bis-phenol pyrazole was identified from hig
- Jain, Rama,Mathur, Michelle,Lan, Jiong,Costales, Abran,Atallah, Gordana,Ramurthy, Savithri,Subramanian, Sharadha,Setti, Lina,Feucht, Paul,Warne, Bob,Doyle, Laura,Basham, Stephen,Jefferson, Anne B.,Lindvall, Mika,Appleton, Brent A.,Shafer, Cynthia M.
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p. 6766 - 6783
(2015/09/22)
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein.
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Paragraph 0878; 0879
(2013/03/26)
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- OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION FOR COMBINATION THERAPY
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The present invention relates to combination therapy using compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined herein and an additional pharmaceutically active agent. The invention also relates to pharmaceutical compositions comprising these combinations, and methods of using these combinations in the treatment of various diseases and disorders.
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Paragraph 0280; 0281; 0280
(2013/08/14)
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- Discovery of a novel series of potent and orally bioavailable phosphoinositide 3-kinase γ inhibitors
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The phosphoinositide 3-kinases (PI3Ks) have been linked to an extraordinarily diversified group of cellular functions making these enzymes compelling targets for the treatment of disease. A large body of evidence has linked PI3Kγ to the modulation of autoimmune and inflammatory processes making it an intriguing target for drug discovery. Our high-throughput screening (HTS) campaign revealed two hits that were nominated for further optimization studies. The in vitro activity of the first HTS hit, designated as the sulfonylpiperazine scaffold, was optimized utilizing structure-based design. However, nonoptimal pharmacokinetic properties precluded this series from further studies. An overlay of the X-ray structures of the sulfonylpiperazine scaffold and the second HTS hit within their complexes with PI3Kγ revealed a high degree of overlap. This feature was utilized to design a series of hybrid analogues including advanced leads such as 31 with desirable potency, selectivity, and oral bioavailability.
- Leahy, James W.,Buhr, Chris A.,Johnson, Henry W. B.,Kim, Byung Gyu,Baik, Taegon,Cannoy, Jonah,Forsyth, Timothy P.,Jeong, Joon Won,Lee, Matthew S.,Ma, Sunghoon,Noson, Kevin,Wang, Longcheng,Williams, Matthew,Nuss, John M.,Brooks, Eric,Foster, Paul,Goon, Leanne,Heald, Nathan,Holst, Charles,Jaeger, Christopher,Lam, Scott,Lougheed, Julie,Nguyen, Lam,Plonowski, Arthur,Song, Joanne,Stout, Thomas,Wu, Xiang,Yakes, Michael F.,Yu, Peiwen,Zhang, Wentao,Lamb, Peter,Raeber, Olivia
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experimental part
p. 5467 - 5482
(2012/09/25)
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- OXADIAZOLE INHIBITORS OF LEUKOTRIENE PRODUCTION
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The present invention relates to compound of formula (I): or pharmaceutically acceptable salts thereof, wherein R1-R5 are as defined herein. The invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.
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Page/Page column 136
(2012/03/11)
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