QSAR Study and Molecular Design of Open-Chain Enaminones as Anticonvulsant Agents 英文参考文献.docVIP

Int. J. Mol. Sci. 2011, 12, 9354-9368; doi:10.3390/ijmOPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article QSAR Study and Molecular Design of Open-Chain Enaminones as Anticonvulsant Agents Juan C. Garro Martinez 1,*, Pablo R. Duchowicz 2, Mario R. Estrada 1, Graciela N. Zamarbide 1 and Eduardo A. Castro 2 1 Department of Chemistry, National University of San Luis, Chacabuco 917, San Luis 5700, Argentine; E-Mails: estrada@.ar (M.R.E.); gzama@.ar (G.N.Z.) 2 INIFTA, (CCT-La Plata-CONICET), Diag. 113 y 64, C.C. 16, Suc.4, La Plata 1900, Argentine; E-Mails: pabloducho@ (P.R.D.); eacast@ (E.A.C.) * Author to whom correspondence should be addressed; E-Mail: jcgarro@.ar; Tel./Fax: +54-2652-423789 ext. 122. Received: 15 September 2011; in revised form: 7 November 2011 / Accepted: 24 November 2011 / Published: 14 December 2011 Abstract: Present work employs the QSAR formalism to predict the ED50 anticonvulsant activity of ringed-enaminones, in order to apply these relationships for the prediction of unknown open-chain compounds containing the same types of functional groups in their molecular structure. Two different modeling approaches are applied with the purpose of comparing the consistency of our results: (a) the search of molecular descriptors via multivariable linear regressions; and (b) the calculation of flexible descriptors with the CORAL (CORrelation And Logic) program. Among the results found, we propose some potent candidate open-chain enaminones having ED50 values lower than 10 mg·kg?1 for corresponding pharmacological studies. These compounds are classified as Class 1 and Class 2 according to the Anticonvulsant Selection Project. Keywords: QSAR theory; anticonvulsant activity; open-chain enaminone; flexible descriptors  Int. J. Mol. Sci. 2011, 12 9355 1. Introduction Enaminones are a group of organic compounds carrying the conjugated syste