LIV-3D-QSAR models for PGI2 receptor ligands using multiple conformations.
A new 3D descriptor, the local intersection volume (LIV), was developed by our group and applied to the construction of 3D-QSAR models for ligands of the PGI(2) receptor (IP). The target compounds are a set of 42 aromatic heterocyclic derivatives [Meanwell et al., J. Med. Chem. 36 (1993), 3884], which show agonist activities in the IP receptor and are inhibitors of platelet aggregation. The LIV-3D-QSAR models were obtained through the analysis of 30% of the generated conformations for each compound, using a combined Genetic Algorithm (GA) and Partial Least Square (PLS) approach [Rogers and Hopfinger, J. Inf. Comput. Sci. 34 (1994) 854]. Statistically, Model 3 is the best as well as the most comprehensive in a mechanistic sense. Furthermore, it can be applied to design new IP ligands.
Azevedo Martins
Rita Cristina
RC
Laboratório de Modelagem Molecular (LabMMol), Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universitária, CT, Bloco A, Sala 609, Rio de Janeiro, RJ 21949-900, Brasil.
Girão Albuquerque
Magaly
M
Bicca de Alencastro
Ricardo
R
D000465:Algorithms; D003198:Computer Simulation; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000494:pharmacology*; D016018:Least-Squares Analysis; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D010974:Platelet Aggregation / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D044006:Receptors, Epoprostenol / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
D006571:Heterocyclic Compounds; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D044006:Receptors, Epoprostenol