title: Design, synthesis, binding and docking-based 3D-QSAR studies of 2-pyridylbenzimidazoles--a new family of high affinity CB1 cannabinoid ligands.
abstract: A series of novel 2-pyridylbenzimidazole derivatives was rationally designed and synthesized based on our previous studies on benzimidazole 14, a CB1 agonist used as a template for optimization. In the present series, 21 compounds displayed high affinities with Ki values in the nanomolar range. JM-39 (compound 39) was the most active of the series (KiCB1 = 0.53 nM), while compounds 31 and 44 exhibited similar affinities to WIN 55212-2. CoMFA analysis was performed based on the biological data obtained and resulted in a statistically significant CoMFA model with high predictive value (q2 = 0.710, r2 = 0.998, r2pred = 0.823).
authors.affiliation: Departamento de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Casilla 5030, Avda. Gran Bretaña 1111, Playa Ancha, Valparaíso, Chile.
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Mella-Raipán
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Lagos
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Recabarren-Gajardo
authors.forename: Christian
authors.initials: C
authors.lastname: Espinosa-Bustos
authors.forename: Javier
authors.initials: J
authors.lastname: Romero-Parra
authors.forename: Hernán
authors.initials: H
authors.lastname: Pessoa-Mahana
authors.forename: Patricio
authors.initials: P
authors.lastname: Iturriaga-Vásquez
authors.forename: Carlos David
authors.initials: CD
authors.lastname: Pessoa-Mahana
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D048588:Benzoxazines / Q000737:chemistry; D002186:Cannabinoids / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D009025:Morpholines / Q000737:chemistry; D009281:Naphthalenes / Q000737:chemistry; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*
chemical_list: C479869:2-(2'-pyridyl)benzimidazole; D001562:Benzimidazoles; D048588:Benzoxazines; D002186:Cannabinoids; D008024:Ligands; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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