Design, Synthesis, Binding and Docking-Based 3D-QSAR Studies of 2-Pyridylbenzimidazoles-A New Family of High Affinity CB1 Cannabinoid Ligands

被引：15

作者：

Mella-Raipan, Jaime A. ^{[1
]}

Lagos, Carlos F. ^{[2
]}

Recabarren-Gajardo, Gonzalo ^{[2
]}

Espinosa-Bustos, Christian ^{[2
]}

Romero-Parra, Javier ^{[2
]}

Pessoa-Mahana, Hernan ^{[3
]}

Iturriaga-Vasquez, Patricio ^{[4
]}

David Pessoa-Mahana, Carlos ^{[2
]}

机构：

[1] Univ Valparaiso, Dept Quim & Bioquim, Fac Ciencias, Valparaiso, Chile

[2] Pontificia Univ Catolica Chile, Dept Farm, Fac Quim, Santiago 22, Chile

[3] Univ Chile, Dept Quim Organ & Fis Quim, Fac Quim & Ciencias Farmaceut, Santiago, Chile

[4] Univ Chile, Fac Ciencias, Dept Quim, Santiago, Chile

来源：

MOLECULES | 2013年 / 18卷 / 04期

关键词：

cannabinoid; CB1; receptor; binding; docking; 3D-QSAR; HUMAN-IMMUNODEFICIENCY-VIRUS-(I) PROTEASE INHIBITORS; MOLECULAR-FIELD ANALYSIS; ENDOCANNABINOID SYSTEM; RECEPTOR; PHARMACOLOGY; DERIVATIVES; AGONISTS; ANALOGS; SERIES; COMFA;

D O I：

10.3390/molecules18043972

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 K-i values in the nanomolar range. JM-39 (compound 39) was the most active of the series (K-iCB1 = 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 (q(2) = 0.710, r(2) = 0.998, r(pred)(2) = 0.823).

引用

页码：3972 / 4001

页数：30