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Discovery of (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): metabolically stable γ-secretase Inhibitors that selectively inhibit the production of amyloid-β over Notch.
Probst G, Aubele DL, Bowers S, Dressen D, Garofalo AW, Hom RK, Konradi AW, Marugg JL, Mattson MN, Neitzel ML, Semko CM, Sham HL, Smith J, Sun M, Truong AP, Ye XM, Xu YZ, Dappen MS, Jagodzinski JJ, Keim PS, Peterson B, Latimer LH, Quincy D, Wu J, Goldbach E, Ness DK, Quinn KP, Sauer JM, Wong K, Zhang H, Zmolek W, Brigham EF, Kholodenko D, Hu K, Kwong GT, Lee M, Liao A, Motter RN, Sacayon P, Santiago P, Willits C, Bard F, Bova MP, Hemphill SS, Nguyen L, Ruslim L, Tanaka K, Tanaka P, Wallace W, Yednock TA, Basi GS. Probst G, et al. Among authors: willits c. J Med Chem. 2013 Jul 11;56(13):5261-74. doi: 10.1021/jm301741t. Epub 2013 Jun 20. J Med Chem. 2013. PMID: 23713656
Laminin-411 is a vascular ligand for MCAM and facilitates TH17 cell entry into the CNS.
Flanagan K, Fitzgerald K, Baker J, Regnstrom K, Gardai S, Bard F, Mocci S, Seto P, You M, Larochelle C, Prat A, Chow S, Li L, Vandevert C, Zago W, Lorenzana C, Nishioka C, Hoffman J, Botelho R, Willits C, Tanaka K, Johnston J, Yednock T. Flanagan K, et al. Among authors: willits c. PLoS One. 2012;7(7):e40443. doi: 10.1371/journal.pone.0040443. Epub 2012 Jul 6. PLoS One. 2012. PMID: 22792325 Free PMC article.