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

Journal of Medicinal Chemistry

Volumn 56, Issue 13, 2013, Pages 5261-5274

  Probst, Gary ^a   Aubele, Danielle L ^a   Bowers, Simeon ^a   Dressen, Darren ^a   Garofalo, Albert W ^a   Hom, Roy K ^a   Konradi, Andrei W ^a   Marugg, Jennifer L ^a   Mattson, Matthew N ^a   Neitzel, Martin L ^a   Semko, Chris M ^a   Sham, Hing L ^a   Smith, Jenifer ^a   Sun, Minghua ^a   Truong, Anh P ^a   Ye, Xiaocong M ^a   Xu, Ying Zi ^a   Dappen, Michael S ^a   Jagodzinski, Jacek J ^a   Keim, Pamela S ^a   Peterson, Brian ^a   Latimer, Lee H ^a   Quincy, David ^a   Wu, Jing ^a   Goldbach, Erich ^a   Ness, Daniel K ^a   Quinn, Kevin P ^a   Sauer, John Michael ^a   Wong, Karina ^a   Zhang, Hongbin ^a   Zmolek, Wes ^a   Brigham, Elizabeth F ^a   Kholodenko, Dora ^a   Hu, Kang ^a   Kwong, Grace T ^a   Lee, Michael ^a   Liao, Anna ^a   Motter, Ruth N ^a   Sacayon, Patricia ^a   Santiago, Pamela ^a   Willits, Christopher ^a   Bard, Frédérique ^a   Bova, Michael P ^a   Hemphill, Susanna S ^a   Nguyen, Lam ^a   Ruslim, Lany ^a   Tanaka, Kevin ^a   Tanaka, Pearl ^a   Wallace, William ^a   Yednock, Ted A ^a   Basi, Guriqbal S ^a   more..

^a ELAN PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 [(4 CHLOROPHENYL)SULFONYL] 6 FLUORO 2 METHYL 2,3 DIHYDROQUINOLIN 4(1H) ONE; 10 [(4 CHLOROPHENYL)SULFONYL] 4,5,6,7,8,9 HEXAHYDRO 2H 4,8 EPIMINOCYCLOOCTA(C)PYRAZOLE; 3 (2 BROMO 4,5 DI FLUOROPHENYL) 1 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL] 1H PYRAZOLE 4 CARBALDEHYDE; 3 (2 BROMO 5 FLUOROPHENYL) 1 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL] 1H PYRAZOLE 4 CARBALDEHYDE; 3 [4 CHLORO N (4 FLUOROPHENYL)PHENYLSULFONAMIDO]BUTANOIC ACID; 3 IODO 1 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL] 1H PYRAZOLE 4 CARBALDEHYDE; 4 CYCLOPROPYL 5 [4 (TRIFLUOROMETHYL)PHENYLSULFONYL] 4,5 DIHYDRO 1H PYRAZOLO(4,3 C)QUINOLINE; 4 CYCLOPROPYL 7,8 DIFLUORO 5 (4 FLUOROPHENYLSULFONYL) 2H PYRAZOLO(4,3 C)QUINOLINE; 4 CYCLOPROPYL 7,8 DIFLUORO 5 [4 (TRIFLUOROMETHYL)PHENYLSULFONYL] 4,5 DIHYDRO 1H PYRAZOLO(4,3 C)QUINOLINE; 4 CYCLOPROPYL 7,8 DIFLUORO 5 [4 (TRIFLUOROMETHYL)PHENYLSULFONYL] 4,5 DIHYDRO 2H PYRAZOLO(4,3 C)QUINOLINE; 4 CYCLOPROPYL 8 FLUORO 5 [6 (TRIFLUOROMETHYL)PYRIDIN 3 YLSULFONYL] 2 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL] 4,5 DIHYDRO 2H PYRAZOLO(4,3 C)QUINOLINE; 4 CYCLOPROPYL 8 FLUORO 5 [6 (TRIFLUOROMETHYL)PYRIDIN 3 YLSULFONYL] 4,5 DIHYDRO 2H PYRAZOLO(4,3 C)QUINOLINE; 5 (4 CHLOROPHENYLSULFONYL) 4,5 DIHYDRO 1 H PYRAZOLO(4,3 C)QUINOLINE; 5 (4 CHLOROPHENYLSULFONYL) 7 FLUORO 5,4 DIHYDRO 1H PYRAZOLO(4,3 C)QUINOLINE; 5 (4 CHLOROPHENYLSULFONYL) 8 FLUORO 4,5 DIHYDRO 1H PYRAZOLO(4,3 C )QUINOLINE; 5 [(4 CHLOROPHENYL)SULFONYL] 4,6 DIETHYL 4,5,6,7 TETRAHYDRO 2H PYRAZOLO(4,3 C)PYRIDINE; 5 [(4 CHLOROPHENYL)SULFONYL] 8 FLUORO 4 METHYL 4,5 DIHYDRO 2H PYRAZOLO(4,3 C)QUINOLINE; 6 (TRIFLUOROMETHYL)PYRIDINE 3 SULFONYL CHLORIDE; 7,8 DIFLUORO 4 METHYL 5 [4 (TRIFLUOROMETHYL)PHENYLSULFONYL] 4,5 DIHYDRO 1H PYRAZOLO(4,3 C)QUINOLINE; 8 FLUORO 5 (4 FLUOROPHENYLSULFONYL) 4 METHYL 4,5 DIHYDRO 1H PYRAZOLO(4,3 C)QUINOLINE; AVAGACESTAT; BEGACESTAT; ELND 006; ELND 007; ETHYL 3 IODO 1 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL] 1H PYRAZOLE 4 CARBOXYLATE; ETHYL 5 IODO 1 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL] 1H PYRAZOLE 4 CARBOXYLATE; GAMMA SECRETASE INHIBITOR; N [[3 (2 BROMO 4,5 DIFLUOROPHENYL) 1 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL] 1H PYRAZOL 4 YL](CYCPROPYL)METHYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; SEMAGACESTAT; TERT BUTYL 3 [(4 FLUOROPHENYL)AMINO]BUTANOATE; TERT BUTYL 3 [4 CHLORO N (4 FLUOROPHENYL)PHENYLSULFONAMIDO]BUTANOATE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CEREBROSPINAL FLUID; CHIRALITY; COMPETITIVE INHIBITION; CONTROLLED STUDY; CYCLIZATION; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG GLUCURONIDATION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HYDROGEN BOND; IN VITRO STUDY; LIPOPHILICITY; MOUSE; NONHUMAN; OXIDATION; STRUCTURE ACTIVITY RELATION;

AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; AREA UNDER CURVE; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; DRUG STABILITY; ENZYME INHIBITORS; GENE EXPRESSION; HETEROCYCLIC COMPOUNDS, 3-RING; HOMEODOMAIN PROTEINS; HUMANS; MALE; MICE; MICROSOMES, LIVER; MODELS, CHEMICAL; MOLECULAR STRUCTURE; PYRAZOLES; QUINOLINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, NOTCH; RNA, MESSENGER; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; TIME FACTORS;

EID: 84880171733     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301741t     Document Type: Article

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