959996-52-2Relevant academic research and scientific papers
Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl) phenylsulfonyl)-4,5-dihydro-1 H -pyrazolo[4,3- c ]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4, 5-dihydro-2 H -pyrazolo[4,3- c ]quinoline (ELND007): Metabolically stable γ-Secretase Inhibitors that selectively inhibit the production of amyloid-β over notch
Probst, Gary,Aubele, Danielle L.,Bowers, Simeon,Dressen, Darren,Garofalo, Albert W.,Hom, Roy K.,Konradi, Andrei W.,Marugg, Jennifer L.,Mattson, Matthew N.,Neitzel, Martin L.,Semko, Chris M.,Sham, Hing L.,Smith, Jenifer,Sun, Minghua,Truong, Anh P.,Ye, Xiaocong M.,Xu, Ying-Zi,Dappen, Michael S.,Jagodzinski, Jacek J.,Keim, Pamela S.,Peterson, Brian,Latimer, Lee H.,Quincy, David,Wu, Jing,Goldbach, Erich,Ness, Daniel K.,Quinn, Kevin P.,Sauer, John-Michael,Wong, Karina,Zhang, Hongbin,Zmolek, Wes,Brigham, Elizabeth F.,Kholodenko, Dora,Hu, Kang,Kwong, Grace T.,Lee, Michael,Liao, Anna,Motter, Ruth N.,Sacayon, Patricia,Santiago, Pamela,Willits, Christopher,Bard, Frédérique,Bova, Michael P.,Hemphill, Susanna S.,Nguyen, Lam,Ruslim, Lany,Tanaka, Kevin,Tanaka, Pearl,Wallace, William,Yednock, Ted A.,Basi, Guriqbal S.
, p. 5261 - 5274 (2013/07/26)
Herein, we describe our strategy to design metabolically stable γ-secretase inhibitors which are selective for inhibition of Aβ generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of Aβ generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered Aβ in the CSF of healthy human volunteers.
Fused, Tricyclic Sulfonamide Inhibitors of Gamma Secretase
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Page/Page column 85; 86, (2008/06/13)
The invention provides compounds of formula I: or pharmaceutically salts thereof where R1, R2, and the A, B, and C-rings are as defined herein. Compounds of formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's disease. The invention also encompasses pharmaceutical compositions comprising compounds or salts of formula I, methods of preparing the desired compounds, and methods of treating cognitive disorders, such as Alzheimer's disease, using the compounds or salts of formula I.
