Novel Aminoguanidinoacetic Acid Antidiabetic Agent
J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 8 1229
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using a Beckman 5801 counter with automatic quench cor-
rection. Creatine uptake was determined by dividing the 14C
per tissue culture dish by the specific activity of the incubation
medium and the protein concentration of the cell extract.
Preliminary studies indicated that under these conditions cell
accumulation of [14C]creatine increased as a linear function
of incubation time. The affinity for creatine uptake (KM) was
43 ( 3 µM and the maximum velocity was 8.7 ( 1.3 nmol/h/
mg protein (n ) 6 experiments). Analysis of the kinetics for
cell uptake using a double-reciprocal plot (Lineweaver-Burk)
plot, indicated that compound 1 was a simple competitive
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3).
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Su p p or tin g In for m a tion Ava ila ble: Crystallographic
data for analogue 69; experimental procedures for analogues
8, 9, 13, 15, 18, 22, 23, 31, 32, 39-41, 48, 51, 52, 56-58, 70-
72, 74, 75, 78, and 79. This material is available free of charge
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(41) A description of the crystallography method and results for 69
are available in the Supporting Information.
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