Pharmacophore based three dimensional structure activity relationship studies on a novel series of pyrimidine-7-ones as selective inhibitors of cdk4

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Abstract

Drug discovery based on the pharmacophore searching is used in the leading modification and searching programmes. In this context, it was thought appropriate to extensively perform pharmacophoric searching in our laboratory for identifying an ideal scaffold for designing an anticancer candidate that eventually could emerge out to become a CDK inhibitor. Four feature pharmacophores consisting of a dual hydrogen bond acceptor site, a hydrogen bond donor site and a positive ionic group as characteristic pharmacophoric features were developed for a novel series of pyrimidin-7-ones for the selective inhibition of CDK4. The hypothesis AADP20 resulted in a statistically reliable 3D QSAR model with 0.9586 as R2 (regression coefficient) value and 0.8835 as Q2 (crossed correlation coefficient) was chosen as the significant common hypothesis. The developed model was validated externally by their predictive accuracy on a selected number of test molecules. The squared regression coefficient of 0.89 was observed between literature value and predicted activity values of test molecules and regression coefficient value of 0.96 was observed between the literature value and the predicted activity values of training set molecules. Thus, the QSAR equation was developed and tested sucessfully on the designed molecules.The equation was significant with values of standard deviation at 0.1773, R2 value at 0.9586, stability at 110, Q2 value at 0.8835 and Pearson-r value at 0.9413.The built model could be useful for predicting the structural requirements that supports in the selective inhibition of CDK4.

Original languageEnglish
Pages (from-to)1568-1574
Number of pages7
JournalLatin American Journal of Pharmacy
Volume36
Issue number8
Publication statusPublished - 01-01-2017

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Quantitative Structure-Activity Relationship
Structure-Activity Relationship
Hydrogen
Drug Discovery
Teaching
pyrimidine

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

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title = "Pharmacophore based three dimensional structure activity relationship studies on a novel series of pyrimidine-7-ones as selective inhibitors of cdk4",
abstract = "Drug discovery based on the pharmacophore searching is used in the leading modification and searching programmes. In this context, it was thought appropriate to extensively perform pharmacophoric searching in our laboratory for identifying an ideal scaffold for designing an anticancer candidate that eventually could emerge out to become a CDK inhibitor. Four feature pharmacophores consisting of a dual hydrogen bond acceptor site, a hydrogen bond donor site and a positive ionic group as characteristic pharmacophoric features were developed for a novel series of pyrimidin-7-ones for the selective inhibition of CDK4. The hypothesis AADP20 resulted in a statistically reliable 3D QSAR model with 0.9586 as R2 (regression coefficient) value and 0.8835 as Q2 (crossed correlation coefficient) was chosen as the significant common hypothesis. The developed model was validated externally by their predictive accuracy on a selected number of test molecules. The squared regression coefficient of 0.89 was observed between literature value and predicted activity values of test molecules and regression coefficient value of 0.96 was observed between the literature value and the predicted activity values of training set molecules. Thus, the QSAR equation was developed and tested sucessfully on the designed molecules.The equation was significant with values of standard deviation at 0.1773, R2 value at 0.9586, stability at 110, Q2 value at 0.8835 and Pearson-r value at 0.9413.The built model could be useful for predicting the structural requirements that supports in the selective inhibition of CDK4.",
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