title: 3D-QSAR/CoMFA-based structure-affinity/selectivity relationships of aminoalkylindoles in the cannabinoid CB1 and CB2 receptors.
abstract: A 3D-QSAR (CoMFA) study was performed in an extensive series of aminoalkylindoles derivatives with affinity for the cannabinoid receptors CB1 and CB2. The aim of the present work was to obtain structure-activity relationships of the aminoalkylindole family in order to explain the affinity and selectivity of the molecules for these receptors. Major differences in both, steric and electrostatic fields were found in the CB1 and CB2 CoMFA models. The steric field accounts for the principal contribution to biological activity. These results provide a foundation for the future development of new heterocyclic compounds with high affinity and selectivity for the cannabinoid receptors with applications in several pathological conditions such as pain treatment, cancer, obesity and immune disorders, among others.
authors.affiliation: Departamento de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Playa Ancha, Valparaíso, Casilla 5030, Chile. jaime.mella@uv.cl.
authors.forename: Jaime
authors.initials: J
authors.lastname: Mella-Raipán
authors.affiliation: Departamento de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Playa Ancha, Valparaíso, Casilla 5030, Chile.
authors.forename: Santiago
authors.initials: S
authors.lastname: Hernández-Pino
authors.affiliation: Laboratorio de Bionanotecnología, Departamento de Ciencias Químico Biológicas, Universidad Bernardo O´Higgins, General Gana 1780, Santiago 8370993, Chile.
authors.forename: César
authors.initials: C
authors.lastname: Morales-Verdejo
authors.affiliation: Departamento de Farmacia, Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, 22, Santiago 7820436, Chile.
authors.forename: David
authors.initials: D
authors.lastname: Pessoa-Mahana
mesh_terms: D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D043884:Receptor, Cannabinoid, CB1 / Q000737:chemistry* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2