3D-QSAR of amino-substituted pyrido[3,2B]pyrazinones as PDE-5 inhibitors

Autor: Mymoona Akhtar, Rikta Saha, Omprakash Tanwar, Mohammad Mumtaz Alam
Rok vydání: 2010
Předmět:
Zdroj: Medicinal Chemistry Research. 21:202-211
ISSN: 1554-8120
1054-2523
Popis: A 3D-QSAR study on amino-substituted pyrido[3,2b]pyrazinones as PDE-5 inhibitors was successfully performed by means of pharmacophore mapping using PHASE module of Schrodinger-9. The 3D-QSAR obtained from AADHRR-183 hypothesis was found to be statistically good with r2 = 0.95 and q2 = 0.81 taking PLS factor 4. The statistical significance of the model was also confirmed by a high value of Fisher ratio of 85.1 and a very low value of RMSE 0.29. One of the other parameters which signify the model predictivity is Pearson R. Its value of 0.91 shows that the correlation between predicted and observed activities for the test set compounds is excellent. Hydrophobic groups are important for PDE-5 inhibition while H-bond donor groups are less favorable for the same. Electron withdrawing groups are favorable if include at ring A in the structures while unfavorable at other sites. Thus, it can be assumed that the present QSAR analysis is enough to demonstrate PDE-5 inhibition with the help of AADHRR-183 hypothesis and will help in designing novel and potent PDE-5 inhibitors.
Databáze: OpenAIRE
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