Decreasing the rate of metabolic ketone reduction in the discovery of a clinical acetyl-CoA carboxylase inhibitor for the treatment of diabetes

Journal of Medicinal Chemistry

Volumn 57, Issue 24, 2014, Pages 10512-10526

  Griffith, David A ^a   Kung, Daniel W ^a   Esler, William P ^a   Amor, Paul A ^a   Bagley, Scott W ^a   Beysen, Carine ^c   Carvajal Gonzalez, Santos ^a   Doran, Shawn D ^a   Limberakis, Chris ^a   Mathiowetz, Alan M ^a   McPherson, Kirk ^a   Price, David A ^a   Ravussin, Eric ^b   Sonnenberg, Gabriele E ^a   Southers, James A ^a   Sweet, Laurel J ^a   Turner, Scott M ^c   Vajdos, Felix F ^a  

^a PFIZER INC   (United States)

^b PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^c KINEMED INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (TERT BUTYL) 1' (1H INDAZOLE 5 CARBONYL) 1,4 DIHYDROSPIRO[INDAZOLE 5,4' PIPERIDIN] 7(6H) ONE; 1 ETHYL 1' (1H INDAZOLE 5 CARBONYL) 1,4 DIHYDROSPIRO[INDAZOLE 5,4' PIPERIDIN] 7(6H) ONE; 1 ISOPROPYL 1' (1H PYRROLO[3,2 B]PYRIDINE 6 CARBONYL) 1,4 DIHYDROSPIRO[INDAZOLE 5,4' PIPERIDIN] 7(6H) ONE; 1 ISOPROPYL 1' (2 METHYL 1H BENZO[D]IMIDAZOLE 6 CARBONYL) 1,4 DIHYDROSPIRO[INDAZOLE 5,4' PIPERIDIN] 7(6H) ONE; 1' (1H INDAZOLE 5 CARBONYL) 1 ISOPROPYL 1,4 DIHYDROSPIRO[INDAZOLE 5,4' PIPERIDIN] 7(6H) ONE; 2' (TERT BUTYL) 1 (1H INDAZOLE 5 CARBONYL) 6' METHYL 2'H SPIRO[PIPERIDINE 4,5' PYRANO[3,2 C]PYRAZO] 7' (6'H) ONE; 2' (TERT BUTYL) 1 (1H INDAZOLE 5 CARBONYL) 6',6' DIMETHYL 2'H SPIRO[PIPERIDINE 4,5' PYRANO[3,2 C]]PYRANO] 7' (6'H) ONE; ACETYL COENZYME A CARBOXYLASE INHIBITOR; ANTIDIABETIC AGENT; KETONE; LIGASE INHIBITOR; MALONYL COENZYME A; UNCLASSIFIED DRUG; [2' (TERT BUTYL) 7' HYDROXY 6',6' DIMETHYL 6',7' DIHYDRO 2'H SPIRO(PIPERIDINE 4,5' PYRANO[3,2 C]PYRAZOL) 1 YL](1H INDAZOL 5 YL) METHANONE; [2' (TERT BUTYL) 7' HYDROXY 6',7' DIHYDRO 2'H SPIRO(PIPERIDINE 4,5' PYRANO[3,2 C]PYRAZO) 1 YL]; ACETYL COENZYME A CARBOXYLASE;

ANIMAL CELL; ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CALORIMETRY; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG HALF LIFE; DRUG SOLUBILITY; DRUG SYNTHESIS; ENZYME INHIBITION; FATTY ACID OXIDATION; HUMAN; HYDROGEN BOND; LIPOGENESIS; LIVER CELL; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; RAT; REDUCTION; SINGLE DRUG DOSE; STEREOSPECIFICITY; X RAY CRYSTALLOGRAPHY; ADULT; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CHEMICAL STRUCTURE; COMPARATIVE STUDY; CROSSOVER PROCEDURE; CYTOLOGY; DIABETES MELLITUS, TYPE 2; DOG; DOUBLE BLIND PROCEDURE; DRUG EFFECTS; METABOLISM; MICROSOME; MIDDLE AGED; RANDOMIZED CONTROLLED TRIAL; SPRAGUE DAWLEY RAT; STRUCTURE ACTIVITY RELATION; WISTAR RAT; YOUNG ADULT;

ACETYL-COA CARBOXYLASE; ADULT; ANIMALS; AREA UNDER CURVE; CELLS, CULTURED; CROSS-OVER STUDIES; DIABETES MELLITUS, TYPE 2; DOGS; DOUBLE-BLIND METHOD; HEPATOCYTES; HUMANS; KETONES; LIPOGENESIS; MALE; MALONYL COENZYME A; MICROSOMES; MIDDLE AGED; MODELS, MOLECULAR; MOLECULAR STRUCTURE; RATS; RATS, SPRAGUE-DAWLEY; RATS, WISTAR; STRUCTURE-ACTIVITY RELATIONSHIP; YOUNG ADULT;

EID: 84920165024     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5016022     Document Type: Article

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