Journal of Computer-Aided Molecular Design

, Volume 21, Issue 5, pp 251–267

Optimization of biaryl piperidine and 4-amino-2-biarylurea MCH1 receptor antagonists using QSAR modeling, classification techniques and virtual screening

  • Georgia Melagraki
  • Antreas Afantitis
  • Haralambos Sarimveis
  • Panayiotis A. Koutentis
  • John Markopoulos
  • Olga Igglessi-Markopoulou
Original Paper

DOI: 10.1007/s10822-007-9112-4

Cite this article as:
Melagraki, G., Afantitis, A., Sarimveis, H. et al. J Comput Aided Mol Des (2007) 21: 251. doi:10.1007/s10822-007-9112-4

Abstract

This paper presents the results of an optimization study on biaryl piperidine and 4-amino-2-biarylurea MCH1 receptor antagonists, which was accomplished by using quantitative-structure activity relationships (QSARs), classification and virtual screening techniques. First, a linear QSAR model was developed using Multiple Linear Regression (MLR) Analysis, while the Elimination Selection-Stepwise Regression (ES-SWR) method was adopted for selecting the most suitable input variables. The predictive activity of the model was evaluated using an external validation set and the Y-randomization technique. Based on the selected descriptors, the Support Vector Machines (SVM) classification technique was utilized to classify data into two categories: “actives” or “non-actives”. Several attempts were made to optimize the scaffold of most potent compounds by inducing various structural modifications. Potential derivatives with improved activities were identified, as they were classified “actives” by the SVM classifier. Their activities were estimated using the produced MLR model. A detailed analysis on the model applicability domain defined the compounds, whose estimations can be accepted with confidence.

Keywords

MCH1R QSAR Classification SVM Virtual screening 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Georgia Melagraki
    • 1
  • Antreas Afantitis
    • 1
    • 2
  • Haralambos Sarimveis
    • 1
  • Panayiotis A. Koutentis
    • 3
  • John Markopoulos
    • 4
  • Olga Igglessi-Markopoulou
    • 1
  1. 1.School of Chemical EngineeringNational Technical University of AthensAthensGreece
  2. 2.Department of ChemoInformaticsNovaMechanics LtdLarnacaCyprus
  3. 3.Department of ChemistryUniversity of CyprusNicosiaCyprus
  4. 4.Department of ChemistryUniversity of AthensAthensGreece