CoMFA and CoMSIA analyses on 4-oxo-1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine derivatives as selective CB2 receptor agonists
| Autor: | Sara Cesarini, Paola Fossa, Luisa Mosti, Elena Cichero |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Quantitative structure–activity relationship CoMFA Stereochemistry Quantitative Structure-Activity Relationship Cb2 agonist 4-dihydro-1 Catalysis Receptor Cannabinoid CB2 Inorganic Chemistry Cannabinoid receptor type 2 Humans Naphthyridines Physical and Theoretical Chemistry 5 Chemistry CoMSIA 4-oxo-1 4-dihydroquinoline derivatives 1 6- and -1 8-naphthyridine derivatives CB2 receptor agonists Organic Chemistry Order (ring theory) Computer Science Applications Computational Theory and Mathematics Quinolines Selectivity Protein Binding |
| Zdroj: | Journal of Molecular Modeling. 16:677-691 |
| ISSN: | 0948-5023 1610-2940 |
| DOI: | 10.1007/s00894-009-0580-4 |
| Popis: | Novel classes of CB2 agonists based on 4-oxo-1,4-dihydroquinoline and 4-oxo-1,4-dihydro-1,5-, -1,6- and -1,8-naphthyridine scaffolds have shown high binding affinity toward CB2 receptor and good selectivity over CB1. A computational study of comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was performed, in order to identify the key structural features impacting their binding affinity. The final CoMSIA model resulted to be the more predictive, showing \( r_{ncv}^2 = 0.84 \), \( r_{cv}^2 = ~0.619 \), SEE = 0.369, and \( r_{pred}^2 = 0.75 \). The study provides useful suggestions for the synthesis of new selective analogues with improved affinity. |
| Databáze: | OpenAIRE |
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