Abstract:
:A set of forty-seven Akt1 inhibitors was used for the development of molecular docking based QSAR model by using nonlinear regression. The integration of docking scores, key interaction profiles and molecular descriptors remarkably improved the accuracy of the QSAR models, providing reasonable statistical parameters (Rtrain(2) = 0.948, Rtest(2) = 0.907 and Qcv(2) = 0.794). The established MD-SVR model based structural modification of new 4-amino-pyrimidine derivatives was further performed, and six compounds 56a,b and 60a-d with good prediction activities were synthesized and biologically evaluated. All of these compounds exhibited promising Akt1 inhibitory and antiproliferative activities, suggesting the reliability and good application value of the established MD-SVR model in the development of Akt1 inhibitors.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Zhan W,Li D,Che J,Zhang L,Yang B,Hu Y,Liu T,Dong Xdoi
10.1016/j.ejmech.2014.01.019subject
Has Abstractpub_date
2014-03-21 00:00:00pages
11-20eissn
0223-5234issn
1768-3254pii
S0223-5234(14)00050-6journal_volume
75pub_type
杂志文章abstract::Some aryl substituted terpenyl pyrimidines 4 (a-p) have been synthesized using novel synthetic methods. The compounds were screened for in vitro antileishmanial activity against promastigotes. Compounds 4c, 4i and 4l showed IC(50) values as 35, 35 and 25 microg ml(-1). ...
journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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journal_title:European journal of medicinal chemistry
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