Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK)

Journal of Medicinal Chemistry

Volumn 60, Issue 18, 2017, Pages 7835-7849

  Huard, Kim ^a   Ahn, Kay ^a,b   Amor, Paul ^a   Beebe, David A ^a   Borzilleri, Kris A ^a   Chrunyk, Boris A ^a   Coffey, Steven B ^a   Cong, Yang ^a   Conn, Edward L ^a   Culp, Jeffrey S ^a   Dowling, Matthew S ^a   Gorgoglione, Matthew F ^a   Gutierrez, Jemy A ^a   Knafels, John D ^a   Lachapelle, Erik A ^a   Pandit, Jayvardhan ^a   Parris, Kevin D ^a   Perez, Sylvie ^a   Pfefferkorn, Jeffrey A ^a   Price, David A ^a   Raymer, Brian ^a   Ross, Trenton T ^a   Shavnya, Andre ^a   Smith, Aaron C ^a   Subashi, Timothy A ^a   Tesz, Gregory J ^a   Thuma, Benjamin A ^a   Tu, Meihua ^a   Weaver, John D ^a   Weng, Yan ^a   Withka, Jane M ^a   Xing, Gang ^a   Magee, Thomas V ^a   more..

^a PFIZER INC   (United States)

^b JANSSEN RESEARCH AND DEVELOPMENT   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

1 CYANO 3,3,3 TRIFLUOROPROP 1 EN 2 YL 4 METHYLBENZENESULFONATE; 2 (3 HYDROXY 3 METHYLPYRROLIDIN 1 YL) 6 [4 (2 HYDROXYETHYL)PIPERAZIN 1 YL] 4 (TRIFLUOROMETHYL)NICOTINONITRILE; 2 CHLORO 6 (4 (2 HYDROXYETHYL)PIPERAZIN 1 YL) 4 (TRIFLUOROMETHYL)NICOTINONITRILE; 2 ETHYL 7 (3 HYDROXY 3 METHYLPYRROLIDIN 1 YL) 5 (TRIFLUOROMETHYL) 1H PYRROLO[3,2 B]PYRIDINE 6 CARBONITRITE; 2 ETHYL 7 HYDROXY 5 (TRIFLUOROMETHYL) 1H PYRROLO[3,2 B]PYRIDINE 6 CARBONITRILE; 6 (3,4 DIHYDROXYPYRROLIDIN 1 YL) 2(3 HYDROXY 3 METHYLPYRROLIDIN 1 YL) 4 (TRIFLUOROMETHYL)NICOTINONITRILE; 6 [4 (2 HYDROXYETHYL)PIPERAZIN 1 YL] 2 [3 (HYDROXYMETHYL)PIPERIDIN 1 YL] 4 (TRIFLUOROMETHYL)NICOTINONITRILE; 7 (3 HYDROXY 3 METHYLPYRROLIDIN 1 YL) 5 (TRIFLUOROMETHYL) 1H PYRROLO[3,2 B] PYRIDINE 6 CARBONITRILE; 7 (3 HYDROXY 3 METHYLPYRROLIDIN 1 YL) 5 (TRIFLUOROMETHYL) 1H PYRROLO[3,2 B]PYRIDINE 6 CARBONITRILE; 7 HYDROXY 5 (TRIFLUOROMETHYL) 1H PYRROLO[3,2 B]PYRIDINE 6 CARBONITRILE; ETHYL 3 AMINO 5 ETHYL 1H PYRROLE 2 CARBOXYLATE; FRUCTOSE; KETOHEXOKINASE; PENT 2 YNENITRILE; PHOSPHOTRANSFERASE INHIBITOR; PYRIDINE; SMALL MOLECULE TRANSPORT AGENT; UNCLASSIFIED DRUG; [1 (5 METHYL 7H PYRROLO[2,3 D]PYRIMIDIN 4 YL)PIPERIDIN 3 YL]METHANOL; FRUCTOKINASE; MOLECULAR LIBRARY; PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG DESIGN; DRUG INHIBITION; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; ENZYME INHIBITION; FRUCTOSE METABOLISM; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; NONHUMAN; RAT; REACTION OPTIMIZATION; SPRAGUE DAWLEY RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; METABOLISM; MOLECULAR DOCKING; MOLECULAR LIBRARY; PHARMACOLOGY; X RAY CRYSTALLOGRAPHY;

ANIMALS; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; FRUCTOKINASES; HUMANS; MALE; MOLECULAR DOCKING SIMULATION; PROTEIN KINASE INHIBITORS; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY; SMALL MOLECULE LIBRARIES;

EID: 85030242549     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.7b00947     Document Type: Article

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