Synthesis and Biological Evaluation of Phthalazinone Inhibitors of ...

Table II. Van der Waals radii distances and Conformations between functional
groups.
Cmpd
Å
Cl, F(25) Cl, F(26) Cl, F(27) vdW Sum Conf.
30 3.03 4.41 3.06 3.22
Gauche -
Cl, F(25),
F(27)
O, F(26) O, F(27) O, F(28) vdW Sum Conf.
34
4.09 2.71 2.91 2.99
Gauche -
F(28), F(27),
O
C, F(26) C, F(27) C, F(28) vdW Sum Conf.
5.48 4.03 4.12 3.17
Out of plane -
C
ChemBio3D Ultra was used to energy minimize 30 (3-CF3-4-ClPh) and 34 (3-
CF3-4-OMePh) for the van der Waals radii distances, molecular conformations, and
pseudo-ring formations. The distances between F(25) and F(27) of the
trifluoromethyl group and the chlorine of 30 are significantly less than the sum of
the van der Waals radii (3.22 Å) 11 and indicates presence of an interaction between
the elements.
In compound 34 (3-CF3-4-OMePh), the distance between two of the fluorines
of the trifluoromethyl group and the ether are less than the sum of their Van der
Waals radii (2.99 Å) 11 ; similarity in distance (2.74 Å, 2.87 Å) suggests gauche
conformation. As predicted, the distance between the fluorines of the
trifluoromethyl group and the methyl of the methoxy group are greater than van der
Waals radii (3.17 Å). We believe the lack of inhibitory activity of 34 and similar
compounds is due to the out-of-plane conformation of groups like the methyl of
12