Discovery of highly potent and selective small molecule ADAMTS-5 inhibitors that inhibit human cartilage degradation via encoded library technology (ELT)

Journal of Medicinal Chemistry

Volumn 55, Issue 16, 2012, Pages 7061-7079

  Deng, Hongfeng ^a   O'Keefe, Heather ^a   Davie, Christopher P ^a   Lind, Kenneth E ^a   Acharya, Raksha A ^a,b   Franklin, G Joseph ^a   Larkin, Jonathan ^a   Matico, Rosalie ^a   Neeb, Michael ^a   Thompson, Monique M ^a   Lohr, Thomas ^a   Gross, Jeffrey W ^a   Centrella, Paolo A ^a,c   O'Donovan, Gary K ^a   Bedard, Katie L ^a   Van Vloten, Kurt ^a,d   Mataruse, Sibongile ^a   Skinner, Steven R ^a   Belyanskaya, Svetlana L ^a   Carpenter, Tiffany Y ^a   Shearer, Todd W ^a   Clark, Matthew A ^a,c   Cuozzo, John W ^a,c   Arico Muendel, Christopher C ^a   Morgan, Barry A ^a   more..

^a GLAXOSMITHKLINE   (United States)

^b EnVivo Pharmaceuticals   (United States)

^c X Chem Incorporated   (United States)

^d BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 FLUORO 4 METHYL N [1 [4 [[2 (NAPHTHALEN 1 YL)ETHYL]AMINO] 6 [(2 OXOAZEPAN 3 YL)AMINO] 1,3,5 TRIAZIN 2 YL]PYRROLIDIN 3 YL]BENZENESULFONAMIDE; ADAMTS1 PROTEIN; AGGRECAN; AGGRECANASE 1; AGGRECANASE 2; CHLOROTRIANISENE; COLLAGENASE 3; GLYCOSAMINOGLYCAN; INTERLEUKIN 1BETA; METALLOPROTEINASE INHIBITOR; N [1 [4 (BENZYLAMINO) 6 [(2 OXOAZEPAN 3 YL)AMINO] 1,3,5 TRIAZIN 2 YL]PYRROLIDIN 3 YL] 3 FLUORO 4 METHYLBENZENESULFONAMIDE; N [[1 [4 (3 BUTEN 1 YLAMINO) 6 [[[2 (2 THIENYL) 1,3 THIAZOL 4 YL]METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 2 NAPHTHALENESULFONAMIDE; N [[1 [4 (3 BUTEN 1 YLAMINO) 6 [[[2 (2 THIENYL) 1,3 THIAZOL 4 YL]METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; N [[1 [4 (BUT 3 EN 1 YLAMINO) 6 [[[2 (THIOPHEN 2 YL)THIAZOL 4 YL]METHYL]AMINO] 1,3,5 TRIAZIN 2 YL]PYRROLIDIN 2 YL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 (BUTYLAMINO) 6 [[(1 METHYL 1H IMIDAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 (BUTYLAMINO) 6 [[[2 (2 THIENYL) 1,3 THIAZOL 4 YL]METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; N [[1 [4 (CYCLOPENTYLAMINO) 6 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 (CYCLOPROPYLAMINO) 6 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 (METHYLAMINO) 6 [[[2 (2 THIENYL) 1,3 THIAZOL 4 YL]METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; N [[1 [4 [(2 CYANOETHYL)AMINO] 6 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 [(2 CYCLOPROPYLETHYL)AMINO] 6 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 [(2 HYDROXYETHYL)AMINO] 6 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 [(2 METHYLPROPYL)AMINO] 6 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 [(CYCLOPROPYLMETHYL)AMINO] 6 [[[2 (2 THIENYL) 1,3 THIAZOL 4 YL]METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; N [[1 [4 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 6 (PROPYLAMINO) 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 [[[2 (2 THIENYL) 1,3 THIAZOL 4 YL]METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; N [[1 [4 [METHYL(PROPYL)AMINO] 6 [[(2 PHENYL 1,3 THIAZOL 4 YL)METHYL]AMINO] 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 PROPYLBENZENESULFONAMIDE; N [[1 [4 OXO 6 [[[2 (2 THIENYL) 1,3 THIAZOL 4 YL]METHYL]AMINO] 1,4 DIHYDRO 1,3,5 TRIAZIN 2 YL] 2 PYRROLIDINYL]METHYL] 4 (TRIFLUOROMETHYL)BENZENESULFONAMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VON WILLEBRAND FACTOR CLEAVING PROTEINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CARTILAGE DEGENERATION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG INHIBITION; DRUG STRUCTURE; DRUG SYNTHESIS; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; OSTEOARTHRITIS; RAT; STRUCTURE ACTIVITY RELATION;

ADAM PROTEINS; AGGRECANS; ANIMALS; CARTILAGE, ARTICULAR; DATABASES, CHEMICAL; ENDOPEPTIDASES; EPITOPES; GLYCOSAMINOGLYCANS; HUMANS; MALE; MIDDLE AGED; OSTEOARTHRITIS; RATS; RATS, SPRAGUE-DAWLEY; SMALL MOLECULE LIBRARIES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES; TRIAZINES;

EID: 84866910785     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300449x     Document Type: Article

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