Identification of potent and selective hydantoin inhibitors of aggrecanase-1 and aggrecanase-2 that are efficacious in both chemical and surgical models of osteoarthritis

Journal of Medicinal Chemistry

Volumn 57, Issue 24, 2014, Pages 10476-10485

  Durham, Timothy B ^a   Klimkowski, Valentine J ^a   Rito, Christopher J ^a   Marimuthu, Jothirajah ^a   Toth, James L ^a   Liu, Chin ^a   Durbin, Jim D ^a   Stout, Stephanie L ^a   Adams, Lisa ^a   Swearingen, Craig ^a   Lin, Chaohua ^a   Chambers, Mark G ^a   Thirunavukkarasu, Kannan ^a   Wiley, Michael R ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 CHLORO N [[ 2,5 DIOXO 4 THIAZOL 2 YL IMIDAZOLIDIN 4YL]METHYL]BENZOFURAN 2 CARBOXAMIDE; 5 CHLORO N [[ 4 (1 METHYLIMIDAZOL 2 YL) 2,5 DIOXO IMIDAZOLIDIN 4 YL]METHYL]BENZOFURAN 2 CARBOXAMIDE; 5 CHLORO N [[4 (3 METHYL 2 PYRIDYL) 2,5 DIOXO IMIDAZOLIDIN 4 YL]METHYL]BENZOFURAN 2 CARBOXAMIDE; 5 CHLORO N [[4 METHYL 2,5 DIOXO IMIDAZOLIDIN 4 YL]METHYL]BENZOFURAN 2 CARBOXAMIDE; AGGRECANASE 1; AGGRECANASE 2; COLLAGENASE 3; ENZYME INHIBITOR; GELATINASE A; HYDANTOIN DERIVATIVE; MATRIX METALLOPROTEINASE 14; METALLOPROTEINASE; STROMELYSIN; UNCLASSIFIED DRUG; ADAM PROTEIN; ADAMTS5 PROTEIN, RAT; AGGRECANASE-1; BENZOFURAN DERIVATIVE; N-((4-(1-METHYLIMIDAZOL-2-YL)-2,5-DIOXOIMIDAZOLIDIN-4-YL)METHYL)-5-(TRIFLUOROMETHYL)BENZOFURAN-2-CARBOXAMIDE; PROCOLLAGEN N PROTEINASE; PROTEINASE INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; CRYSTAL STRUCTURE; DRUG CLEARANCE; DRUG DESIGN; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SCREENING; HUMAN; IC50; MALE; NONHUMAN; OSTEOARTHRITIS; PHENOTYPE; RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; AUDIOVISUAL EQUIPMENT; CELL CULTURE; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; KNEE MENISCUS; LEWIS RAT; METABOLISM; MICROSOME; PATHOLOGY; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

ADAM PROTEINS; ANIMALS; BENZOFURANS; CELLS, CULTURED; CRYSTALLOGRAPHY, X-RAY; HYDANTOINS; MALE; MENISCI, TIBIAL; MICROSOMES; MODELS, ANATOMIC; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OSTEOARTHRITIS; PROCOLLAGEN N-ENDOPEPTIDASE; PROTEASE INHIBITORS; RATS; RATS, INBRED LEW; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84920187949     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm501522n     Document Type: Article

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