Bioactivation of the 3-amino-6-chloropyrazinone ring in a thrombin inhibitor leads to novel dihydro-imidazole and imidazolidine derivatives: Structures and mechanism using 13C-labels, mass spectrometry, and NMR

Drug Metabolism and Disposition

Volumn 31, Issue 11, 2003, Pages 1437-1447

  Subramanian, Raju ^a   Lin, Charles C ^a   Ho, Jonathan Z ^a   Pitzenberger, Steven M ^a   Silva elipe, Maria V ^b   Gibson, Christopher R ^a   Braun, Matthew P ^a   Yu, Xiao ^a   Yergey, James L ^a   Singh, Rominder ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [6 CHLORO 3 [(2,2 DIFLUORO 2 PYRIDIN 2 YLETHYL)AMINO] 2 OXOPYRAZIN 1(2H) YL] N [(3 FLUOROPYRIDIN 2 YL)METHYL]ACETAMIDE; CARBON; DRUG METABOLITE; FIBRINOLYTIC AGENT; IMIDAZOLE DERIVATIVE; IMIDAZOLINE DERIVATIVE; PYRAZINE DERIVATIVE; THROMBIN INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL; ANIMAL EXPERIMENT; ARTICLE; BILE; BIOTRANSFORMATION; CHEMISTRY; DRUG ACTIVATION; DRUG BIOAVAILABILITY; DRUG EXCRETION; DRUG POTENCY; DRUG STRUCTURE; MALE; MASS SPECTROMETRY; METABOLISM; METHODOLOGY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; RAT; RAT STRAIN; REACTION ANALYSIS; STRUCTURE ANALYSIS;

ANIMALS; BILE; BIOTRANSFORMATION; CARBON ISOTOPES; FIBRINOLYTIC AGENTS; IMIDAZOLES; MAGNETIC RESONANCE SPECTROSCOPY; MALE; PYRAZINES; RATS; RATS, SPRAGUE-DAWLEY; SPECTROMETRY, MASS, SECONDARY ION;

ANIMALIA;

EID: 10744228010     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.31.11.1437     Document Type: Article

References (9)

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2. Burgey CS, Robinson KA, Lyle TA, Sanderson PEJ, Selnick HG, Isaacs RCA, Lewis SD, Lucas BJ, Krueger JA, Singh R, et al. (2003b) Metabolism-directed optimization of 3-aminopyrazinone acetamide thrombin inhibitors. Development of an orally bioavailable series containing P1 and P3 pyridines. J Med Chem 46:461-473.
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