Quantitative structure-activity relationship analysis of 4(3H)-quinazolone derivatives as tyrosine kinase inhibitors by multiple linear regression.
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.
Srivastava
Vikas
V
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Sinha
Deepa
D
Tiwari
Anjani K
AK
Sharma
Himanshu
H
Bala Sharma
Raj
R
Singh
Vinay K
VK
Mishra
Anil K
AK
D000465:Algorithms; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008956:Models, Chemical; D015394:Molecular Structure; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000737:chemistry* / Q000494:pharmacology*; D012044:Regression Analysis; D012984:Software
D004791:Enzyme Inhibitors; D011799:Quinazolines; D011505:Protein-Tyrosine Kinases