Pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidines
J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 17 2741
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docking procedure then selected the best structures and
applied the totality of the binding site. During the docking,
all torsion angles of the side chains on the ligand were allowed
to vary. This docking procedure was followed by another
sequence of CG energy minimization to a gradient threshold
of < 0.1 kcal/mol/Å. Energy minimization of the complexes was
performed using AMBER94 all-atom force field.
The interaction energy values were calculated as follows:
∆E(complex) ) E(complex) - (E(L) + E(receptor)). These energies are not
rigorous thermodynamic quantities, but can only be used to
compare the relative stabilities of the complexes. Conse-
quently, these interaction energy values cannot be used to
calculate binding affinities, since changes in entropy and
solvation effects are not taken into account.
Abbr evia tion s: DMSO, dimethyl sulfoxide; DPCPX, 1,3-
dipropyl-8-cytclopentylxanthine; THF, tetrahydrofurane; CHO
cells, Chinese hamster ovary cells; EDTA, ethylenediaminotet-
raacetate; NECA, 5′-(N-ethylcarbamoyl)adenosine; TLC, thin-
layer chromatography; mp, melting point; EtOAc, ethyl ac-
etate; IR, infrared spectra; NMR, nuclear magnetic resonance;
CDCl3, deuterated chloroform; CHAPS, 3-[(3-chloroamidopro-
pyl)-dimethylammino]-1-propanesulfonate; [125I]AB-MECA,
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[
125I]1-[6-[[(4-amino-3-iodophenyl)methyl]amino]-9H-purin-9-
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yl]-1-deoxy-N-methyl-â-D-ribofuranuronamide; MRE3008-F20,
5-[[(4-methoxyphenyl)amino] carbonyl]amino-8-propyl-2-(2-fu-
ryl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine; SCH58261,
5-amino-2-(2-furyl)-7-(2-phenylethyl)pyrazolo[4,3-e][1,2,4]-
triazolo[1,5-c]pyrimidine.
Ack n ow led gm en t. This work was supported by
MURST (cofin. 2000, ex 40%, prot. n. MM03237197_004)
and MEDCO Res., Triangle Park, NC.
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