title: LIV-3D-QSAR models for PGI2 receptor ligands using multiple conformations.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rita Cristina
authors.initials: RC
authors.lastname: Azevedo Martins
authors.forename: Magaly
authors.initials: M
authors.lastname: Girão Albuquerque
authors.forename: Ricardo
authors.initials: R
authors.lastname: Bicca de Alencastro
mesh_terms: 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
chemical_list: D006571:Heterocyclic Compounds; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D044006:Receptors, Epoprostenol