Summary
The derivation of a new 3D QSAR field based on the electrotopological state (E-state) formalism is described. A complementary index and its associated field, the HE-state, describing the polarity of hydrogens is also defined. These new fields are constructed from a nonempirical index that incorporates electronegativity, the inductive influence of neighboring atoms, and the topological state into a single atomistic descriptor. The classic CoMFA steroid test data set was examined with models incorporating the E-state and HE-state fields alone and in combination with steric, electrostatic and hydropathic fields. The single best model was the E-state/HE-state combination with q2=0.803 (three components) and r2=0.979. Using the E-state and/or HE-state fields with other fields consistently produced models with improved statistics, where the E-state fields provided a significant, if not dominant, contribution.
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References
Kier, L.B. and Hall, L.H., Pharm. Res., 7 (1990) 801.
Hall, L.H. and Kier, L.B., J. Chem. Inf. Comput. Sci., 31 (1991) 76.
Kier, L.B. and Hall, L.H., Adv. Drug Res., 22 (1992) 1.
Joshi, N. and Kier, L.B., Med. Chem. Res., 1 (1993) 409.
Tsantili-Kakoulidou, A., Kier, L.B. and Joshi, N., J. Chim. Phys., 89 (1992) 1729.
Tsantili-Kakoulidou, A. and Kier, L.B., Pharm. Res., 9 (1992) 1321.
Hall, L.H. and Kier, L.B., Med. Chem. Res., 2 (1992) 497.
Hall, L.H., Mohney, B.K. and Kier, L.B., Quant. Struct.-Act. Relatsh., 12 (1993) 44.
CramerIII, R.D., Patterson, D.E. and Bunce, J.D., J. Am. Chem. Soc., 110 (1988) 5959.
Molconn-Z 3.0, Hall Associates Consulting, Quincy, MA, U.S.A.
Molconn-Z 3.0S, EduSoft, LC, Ashland, VA, U.S.A.
SYBYL 6.2, Tripos Inc., St. Louis, MO, U.S.A.
Kellogg, G.E., Semus, S.F. and Abraham, D.J., J. Comput.-Aided Mol. Design, 5 (1991) 545.
Nayak, V.R. and Kellogg, G.E., Med. Chem. Res., 3 (1994) 491.
Abraham, D.J. and Kellogg, G.E., In Kubinyi, H. (Ed.) 3D QSAR in Drug Design: Theory, Methods and Applications, ESCOM, Leiden, The Netherlands, 1993, pp. 506–522.
Kellogg, G.E., Joshi, G.S. and Abraham, D.J., Med. Chem. Res., 1 (1992) 444.
Hinze, J. and Jaffe, H.H., J. Am. Chem. Soc., 84 (1962) 540.
Kier, L.B. and Hall, L.H., J. Pharm. Sci., 70 (1981) 583.
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Kellogg, G.E., Kier, L.B., Gaillard, P. et al. E-state fields: Applications to 3D QSAR. J Computer-Aided Mol Des 10, 513–520 (1996). https://doi.org/10.1007/BF00134175
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DOI: https://doi.org/10.1007/BF00134175