Design and analysis of a combinatorial library of HEPT analogues: comparison of selection methodologies and inspection of the actually covered chemical space.
A large virtual library of 125 396 HEPT analogues, built by combining all fragments present in the published 180-compound HEPT family, has been studied in terms of diversity criteria and the goodness of the 11 available standard diversity selection methods analyzed. All the algorithms under study, except Cell-based Density, have rank above a random selection of compounds, with Optimum and Standard Deviation based Binning and Cell-based Fraction algorithms being the best choices. Furthermore, analysis of the actually tested compounds has been performed to compare the traditional drug discovery methodology versus a rational selection of combinatorial libraries approach.
Pascual
Rosalia
R
Grup d'Enginyeria Molecular, Institut Químic de Sarrià (IQS), Universitat Ramon Llull, Via Augusta 390, E-08017-Barcelona, Spain.
Mateu
Marta
M
Gasteiger
Johann
J
Borrell
José I
JI
Teixidó
Jordi
J