Synthesis and biological activity of peptidyl aldehyde urokinase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 9, 2000, Pages 983-987

  Tamura, Susan Y ^a   Weinhouse, Michael I ^a   Roberts, Christopher A ^a   Goldman, Erick A ^a   Masukawa, Kevin ^a   Anderson, Susanne M ^a   Cohen, Cheryl R ^a   Bradbury, Annette E ^a   Bernardino, Vernon T ^a   Dixon, Steven A ^a   Ma, Michael G ^a   Nolan, Thomas G ^a   Brunck, Terence K ^a  

^a Dendreon   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PEPTIDYL ALDEHYDE UROKINASE INHIBITOR; PLASMINOGEN ACTIVATOR; PLASMINOGEN ACTIVATOR INHIBITOR; PRODRUG; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DELIVERY SYSTEM; DRUG ELIMINATION; DRUG HALF LIFE; DRUG SELECTIVITY; DRUG STABILITY; DRUG SYNTHESIS; ENZYME INHIBITION; GENE SEQUENCE; HUMAN; LIPOPHILICITY; MAXIMUM ALLOWABLE CONCENTRATION; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ALDEHYDES; ANIMALS; AREA UNDER CURVE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DIPEPTIDES; ENZYME INHIBITORS; HALF-LIFE; PLASMIN; PRODRUGS; RATS; TISSUE PLASMINOGEN ACTIVATOR; URINARY PLASMINOGEN ACTIVATOR;

ANIMALIA;

EID: 0034194355     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00149-9     Document Type: Article

References (32)

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30. 50) was determined as described in ref 15a, using the chromogenic substrate S-2444 (L-Pyroglutamyl-glycyl-L-arginine-p-nitroaniline hydrochloride), obtained from DiaPharma Group, Inc. (West Chester, OH). All reactions contained, at final concentration, 0.75 nM urokinase and 250 μM S-2444. The concentrations of plasmin and t-PA and their substrates were as follows: plasmin (1 nM), S-2366 (300 μM), t-PA (1 nM), Pefachrome t-PA (800 μM).
31. The determination of plasma levels in animals was accomplished using solid-phase extraction sample preparation with HPLC mass spectrometry to quantify compound 1a and its prodrugs using methodologies that will be published elsewhere. The data were evaluated for pharmacokinetic parameters using WinNonlin noncompartmental analysis.
32. Compounds 19a-c are isolated as an 85:15 mixture of L-Ala to D-Ala isomers.