A NOVEL QSAR MODEL FOR EVALUATING AND PREDICTING THE INHIBITION ACTIVITY OF H1-RECEPTOR ANTAGONISTS: A SERIES OF THIENOPYRIMIDINE DERIVATIVES
A Quantitative Structure Activity Relationship (QSAR) study has been established using combination of most influencing physiochemical parameters viz. thermodynamic, electronic, geometric & quantum mechanical descriptors, and H1-antihistaminic activity of a series of thienopyrimidines, the novel Histamine H1 receptor antagonists. Genetic function approximation (GFA) technique was used to identify the descriptors that have influence on biological activity. Dipole, AlogP 98, Jurs and LUMO descriptors were found to influence biological activity significantly. Lipophilicity of compounds was found to have a significant role in H1 Histaminic inhibition along with other thermodynamic, spatial and electronic descriptors. Positive contribution of Dipole, AlogP 98 descriptors suggests that molecules with lipophilic-electronic substituents are more likely to improve the potency. Developed models were found to be significant and predictive as evidenced from their internal and external cross-validation statistics.
Keywords: H1-receptor antagonists; thienopyrimidines; molecular descriptor; genetic function approximations; cross-validation; quantitative structure activity relationship
QSAR : Quantitative structure activity relationship
GFAÂ Â Â : Genetic function approximation
LOFÂ Â Â : Friedmanâ€™s lack of fit
VIFÂ Â Â Â : Variance inflation factor
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).