152338-16-4Relevant articles and documents
(S)-N-(5-Chlorothiophene-2-sulfonyl)-β,β-diethylalaninol a Notch-1-sparing γ-secretase inhibitor
Cole, Derek C.,Stock, Joseph R.,Kreft, Anthony F.,Antane, Madelene,Aschmies, Suzan H.,Atchison, Kevin P.,Casebier, David S.,Comery, Thomas A.,Diamantidis, George,Ellingboe, John W.,Harrison, Boyd L.,Hu, Yun,Jin, Mei,Kubrak, Dennis M.,Lu, Peimin,Mann, Charles W.,Martone, Robert L.,Moore, William J.,Oganesian, Aram,Riddell, David R.,Sonnenberg-Reines, June,Sun, Shaiu-Ching,Wagner, Erik,Wang, Zheng,Woller, Kevin R.,Xu, Zheng,Zhou, Hua,Jacobsen, J. Steven
scheme or table, p. 926 - 929 (2009/09/06)
Accumulation of beta-amyloid (Aβ), produced by the proteolytic cleavage of amyloid precursor protein (APP) by β- and γ-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) γ-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-β,β-diethylalaninol 7.b.2 (Aβ 40/42 EC50 = 28 nM), which is efficacious in reduction of Aβ production in vivo.
Discovery of begacestat, a Notch-1-sparing γ-secretase inhibitor for the treatment of Alzheimer's disease
Mayer, Scott C.,Kreft, Anthony F.,Harrison, Boyd,Abou-Gharbia, Magid,Antane, Madelene,Aschmies, Suzan,Atchison, Kevin,Chlenov, Michael,Cole, Derek C.,Comery, Thomas,Diamantidis, George,Ellingboe, John,Fan, Kristi,Galante, Rocco,Gonzales, Cathleen,Ho, Douglas M.,Hoke, Molly E.,Hu, Yun,Huryn, Donna,Jain, Uday,Jin, Mei,Kremer, Kenneth,Kubrak, Dennis,Lin, Melissa,Lu, Peimin,Magolda, Ron,Martone, Robert,Moore, William,Oganesian, Aram,Pangalos, Menelas N.,Porte, Alex,Reinhart, Peter,Resnick, Lynn,Riddell, David R.,Sonnenberg-Reines, June,Stock, Joseph R.,Sun, Shaiu-Ching,Wagner, Erik,Wang, Ting,Woller, Kevin,Xu, Zheng,Zaleska, Margaret M.,Zeldis, Joseph,Zhang, Minsheng,Zhou, Hua,Jacobsen, J. Steven
supporting information; experimental part, p. 7348 - 7351 (2009/12/23)
SAR on HTS hits 1 and 2 led to the potent, Notch-1-sparing GSI 9, which lowered brain Aβ in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had impro
SUBSTITUTED PHENYLSULFONAMIDE INHIBITORS OF BETA AMYLOID PRODUCTION
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Page 57-58, (2010/02/06)
Compounds of Formula I, wherein R1-R8 are defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer’s Disease and Down’s syndrome are described.
