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. Author manuscript; available in PMC: 2009 Sep 25.
Published in final edited form as: Bioorg Med Chem. 2008 Nov 9;17(1):149–164. doi: 10.1016/j.bmc.2008.11.008

Table 4.

Observed and predicted values for TFK-mediated carboxylesterase inhibition using classical QSAR and CoMFA analyses

No. TFK structureb pKia
 log Pc L B5
hiCE
 hCE1
 rCE
Obsd 5 min Obsd 24 h Eq. (7a) Eq. (7b) Eq. (10a) Eq. (10b) Obsd 5 min Obsd 24 h Eq. (8a) Eq. (8b) Eq. (11a) Eq. (11b) Obsd 5 min Obsd 24 h Eq. (9a) Eq. (9b) Eq. (12a) Eq. (12b)
33 graphic file with name nihms98275t2.jpg 7.82 8.27 8.24 8.24 7.71 7.75 7.15 8.13 7.23 7.26 7.11 7.03 6.80 8.48 6.73 6.76 6.84 6.81 6.63 (6.07) 14.38 10.27
34 7.27 9.40 7.07 7.14 6.77 6.86 5.72 9.40 5.87 5.89 5.65 5.64 5.96 8.85 6.24 6.23 5.73 5.84 5.12 (4.43) 14.38 10.27
35 7.49 9.00 7.01 7.08 7.65 7.70 6.13 9.40 5.80 5.81 6.33 6.30 6.82 9.15 6.20 6.19 6.95 6.88 5.04 (4.34) 14.38 10.27
36 6.82 8.34 7.49 7.47 7.08 7.13 6.89 8.40 7.07 7.11 7.02 6.89 6.80 8.55 6.96 7.00 6.88 6.80 5.57 (5.02) 12.33 8.33
37 5.72 9.30 6.32 6.37 6.00 5.90 5.28 9.30 5.71 5.74 5.53 5.46 5.60 8.52 6.13 6.15 5.57 5.66 4.06 (3.37) 12.33 8.33
38 7.10 8.96 6.25 6.32 6.82 6.82 6.10 9.52 5.64 5.67 6.05 6.04 6.66 8.80 6.07 6.09 6.55 6.41 3.98 (3.28) 12.33 8.33
39 7.66 5.69 7.31 7.14 7.94 7.59 6.82 8.64 7.20 7.09 6.63 6.93 6.85 5.49 7.10 7.06 6.85 6.97 5.11 (4.76) 10.27 7.39
40 6.66 8.46 6.74 6.70 6.64 6.67 6.72 8.38 6.55 6.54 6.87 6.75 6.82 8.11 6.72 6.72 6.85 6.75 4.51 (3.96) 10.27 7.39
41 5.62 9.30 5.57 5.60 5.47 5.49 4.83 9.22 5.18 5.17 4.45 4.66 5.31 8.19 5.56 5.56 5.25 5.26 3.00 (2.31) 10.27 7.39
42 graphic file with name nihms98275t3.jpg 5.33 8.24 5.51 5.55 5.64 5.62 5.82 9.22 5.12 5.10 5.62 5.65 5.32 7.43 5.49 5.48 5.67 5.62 2.92 (2.23) 10.27 7.39
43 6.25 8.19 5.99 5.94 6.03 6.30 6.48 8.28 6.20 6.19 6.39 6.58 6.60 8.00 6.39 6.37 6.45 6.62 3.46 (2.90) 8.22 5.96
44 4.17 9.30 4.82 4.84 4.51 4.43 4.10 8.48 4.85 4.82 4.18 4.24 4.64 7.66 4.90 4.89 4.71 4.75 1.95 (1.26) 8.22 5.96
45 4.56 8.43 4.75 4.78 4.68 4.56 5.01 9.15 4.77 4.74 5.16 5.09 4.82 7.46 4.80 4.80 4.98 4.95 1.87 (1.17) 8.22 5.96
46 5.04 8.92 5.45 5.43 5.38 4.99 5.48 9.00 5.57 5.55 5.87 5.37 5.57 8.77 5.76 5.74 5.79 5.51 2.76 (2.14) 8.22 5.96
47 5.77 7.78 5.23 5.17 5.44 5.64 6.10 8.27 5.85 5.82 6.02 6.16 6.38 8.11 5.84 5.79 6.07 6.21 2.40 (1.84) 6.17 4.54
48 6.12 8.32 5.59 5.54 5.89 6.19 6.92 8.19 6.62 6.69 6.51 6.79 6.39 8.26 6.54 6.57 6.37 6.50 2.91 (2.35) 8.33 3.58
49 4.29 6.93 4.37 4.39 4.07 4.06 4.86 8.22 5.19 5.24 5.02 4.84 4.87 6.97 4.77 4.82 4.71 4.66 1.32 (0.62) 8.33 3.58
a

The experimental Ki values (Obsd) are from Wadkins.27 Predicted Ki values for the classical QSAR are based upon Eq. (7a),Eq. (8a), and Eq. (9a) for gem-diol geometry and Eq. (7b),Eq. (8b), and Eq. (9b) for ketone geometry. Predicted Ki values for the 3D-QSAR are based upon Eq. (10a),Eq. (11a), and Eq. (12a) for gem-diol geometry and Eq. (10b),Eq. (11b), and Eq. (12b) for ketone geometry.

b

TFK structures are drawn as shown in Wadkins27, in which the hydration of the gem-diol/ketone is shown based upon 1H NMR observations. However, the compounds exist in a dynamic equilibrium between ketone and gem-diol in solution.

c

The log P value for the ketone is the first value and the gem-diol is given in parentheses.