title: A CoMSIA study on the adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside analogues.
abstract: The structural requirements of pyrrolo[2,3-d]pyrimidine nucleoside (PPN) analogues as adenosine kinase (AK) inhibitors were in silico studied by using CoMSIA method. All models were trained with 32 compounds, after which they were evaluated for predictive ability with additional 5 compounds. Quantitative information on structure-activity trends is provided for further rational development and direction of selective synthesis. The best CoMSIA model included hydrophobic, H-bond donor and H-bond acceptor fields and had a good predictive quality according to internal validation criteria. In addition, this model predicted adequately the compounds contained in the test set. The analysis of the model gives a comprehensive qualitative and quantitative description of the molecular features at C4 and C5 positions of the pyrrolo[2,3-d]pyrimidine scaffold and C5-position of the beta-d-ribofuranose of PPN analogues, relevant for a high AK inhibitory activity.
authors: Centro de Bioinformática y Simulación Molecular, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile. jcaballero@utalca.cl
authors: Julio
authors: J
authors: Caballero
authors: Michael
authors: M
authors: Fernández
authors: Fernando D
authors: FD
authors: González-Nilo
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D003198:Computer Simulation; D016208:Databases, Factual; D004791:Enzyme Inhibitors; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D009705:Nucleosides; D011743:Pyrimidines; D011758:Pyrroles; C450639:Pyrrolo(2,3-d)pyrimidine; D000248:Adenosine Kinase