Quantitative structure-activity relationships of N2-phenylguanines as inhibitors of herpes simplex virus thymidine kinases.

摘要: Quantitative structure-activity relationships of the Hansch-type were developed to account for inhibition thymidine kinases from Herpes simplex viruses types 1 and 2 (HSV1,2) by N2-phenylguanines. Derivatives with meta and/or para substituents on phenyl ring display a wide range overlapping, but not identical, potencies as inhibitors enzymes. IC50 values 36 (HSV1) 35 (HSV2) used develop equations using hydrophobic (pi), electronic (sigma, R), group size (MR) parameters. Equations correlation coefficients 0.797 0.805, respectively, obtained Potencies correlated positively pi negatively in ring. Positive correlations also resonance parameter R sigma constants substituents. The most potent inhibitor both enzymes was N2-[m-(trifluoromethyl)phenyl]guanine, although HSV2 kinase more sensitive certain compounds than HSV1 enzyme.