Secondary amides of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid as inhibitors of pyruvate dehydrogenase kinase

Journal of Medicinal Chemistry

Volumn 43, Issue 2, 2000, Pages 236-249

  Aicher, Thomas D ^a   Anderson, Robert C ^a,c   Gao, Jiaping ^a   Shetty, Suraj S ^a   Coppola, Gary M ^a   Stanton, James L ^a   Knorr, Douglas C ^a   Sperbeck, Donald M ^a   Brand, Leonard J ^a   Vinluan, Christine C ^a,b   Kaplan, Emma L ^a,b   Dragland, Carol J ^a,b   Tomaselli, Hollis C ^a   Islam, Amin ^a   Lozito, Robert J ^a   Liu, Xilin ^a   Maniara, Wieslawa M ^a   Fillers, William S ^a,b,d   Dominick Delgrande, R ^a   Walter, Eric ^a   Mann, William R ^a,b   more..

^a NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^b Metab Cardiovasc Dis Research   (United States)

^c Sphinx Pharmaceuticals   (United States)

^d BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 N [2,5 DIMETHYL 4 N (4 CYANOBENZOYL)PIPERAZINE] 3,3,3 TRIFLUORO 2 HYDROXY 2 METHYLPROPANAMIDE; N' METHYL N (4 TERT BUTYL 1,2,5,6 TETRAHYDROPYRIDINE)THIOUREA; PIPERAZINE DERIVATIVE; PROTEIN KINASE INHIBITOR; PYRUVATE DEHYDROGENASE; UNCLASSIFIED DRUG;

ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DIABETES MELLITUS; DRUG BIOAVAILABILITY; DRUG EFFECT; ENZYME ASSAY; EXPERIMENTAL MODEL; FIBROBLAST CULTURE; GLUCOSE BLOOD LEVEL; HUMAN; HUMAN CELL; LACTATE BLOOD LEVEL; MALE; NONHUMAN; RAT;

AMIDES; ANIMALS; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; ENZYME INHIBITORS; HUMANS; LACTIC ACID; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICE; MICE, INBRED C57BL; PROPIONIC ACIDS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; RATS; RATS, SPRAGUE-DAWLEY;

EID: 0034719322     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm990358+     Document Type: Article

References (86)

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82. The compounds of this report do not inhibit any enzymes other than PDHKto the best of our knowledge. Other enzymes profiled include Ser/Thr/Tyr kinases (i.e., cAMPk or p38Map kinase) and KATP channels (see ref 31).
83. This crude oil was of sufficient purity to be tested in the primary enzymatic assay. The resulting ICso's of crude substances made this way were in acceptable agreement (within 25%; i.e., 40 nM vs 50 nM) with the values of the purified substances. All IC1S reported within this paper are of purified substances.
84. 50 for 14e remains as it is in the primary enzymatic assay (see ref 35 for the details of this assay).
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86. Male ZDF rats at 8 weeks of age in groups of 6 were profiled via this same procedure.