Applications of Bond‐Based 3D‐Chiral Quadratic Indices in QSAR Studies Related to Central Chirality Codification
Juan A. Castillo‐Garit, Yovani Marrero‐Ponce, Francisco Torrens, Ramón García‐Domenech, José Enrique Rodríguez-Borges · QSAR & Combinatorial Science · 2009
Abstract The concept of bond‐based quadratic indices is generalized to codify chemical structure information for chiral drugs, making use of a trigonometric 3D‐chirality correction factor. In order to evaluate the effectiveness of this novel approach in drug design, we have modeled several well‐known data sets. In particularly, Cramer's steroid data set has become a benchmark for the assessment of novel QSAR methods. This data set has been used by several researchers using 3D‐QSAR approaches. Therefore, it is selected by us for the shake of comparability. In addition, to evaluate the effectiveness of this novel approach in drug design, we model the angiotensin‐converting enzyme inhibitory activity of perindoprilate's σ‐stereoisomers combinatorial library, as well as codify information related to a pharmacological property, highly dependent on the molecular symmetry, of a set of seven pairs of chiralN‐alkylated 3‐(3‐hydroxyphenyl)‐piperidines, which bind σ‐receptors. The validation of this method is achieved by comparison with earlier publications applied to the same data sets. The nonstochastic and stochastic bond‐based 3D‐chiral quadratic indices appear to provide a rather interesting alternative to other more common 3D‐QSAR descriptors.