Quantitative Structure–Activity Relationship Analysis of 4(3H)-Quinazolone Derivatives as Tyrosine Kinase Inhibitors by Multiple Linear Regression

Abstract

Computational chemistry is playing an increasingly important role in drug design and discovery, structural biology, and quantitative structure-activity relationship studies. A series of 4(3H)-quinozolone derivatives were screened for two-dimensional quantitative structure-activity relationship studies and subsequently their absorption, distribution, metabolism, and excretion (ADME) properties with the use of soft modeling techniques after selecting suitable descriptors for molecular structure. Multiple linear regression analysis was performed for this study. The final quantitative structure-property relationship mathematical models were found as follows: Equation [Y= log (1MIC)] [symbol: see the text] pMIC= 1. 0:2165κ(1) - 2.082χ(3) - 0.3235μT - 0.2185μx - 100.6qN - 35.42. 2. 0:2185κ(1) - 2.1575χ(3) - 0.3622μT - 0.2142μx - 100.4qN - 31.25. 3. 0:0015ω - 2.0822χ(3) - 0.1252μT - 0.2180μx - 112.9qN - 36.05. 4. 2:108χ(3) - 0.0035ET - 0.2033μx - 3.489qesp - 92.60qN - 33.20. 5. 0:2140κ(1) - 2.186χ(3) - 0.0036Oxxx - 0.0016Oxyy - 78.02qN - 31.52.