2D-QSAR and 3D-QSAR/CoMFA analyses of the N-terminal substituted anthranilic acid based CCK(1) receptor antagonists: 'Hic Rhodus, hic saltus'
| Autor: | Michela V. Pavan, Antonio Varnavas, Lucia Lassiani, Dimitra Hadjipavlou-Litina, Paolo Braiuca |
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| Přispěvatelé: | DIMITRA HADJIPAVLOU, Litina, Paolo, Braiuca, Lassiani, Lucia, MICHELA V., Pavan, Varnavas, Antonios |
| Rok vydání: | 2009 |
| Předmět: |
Steric effects
Models Molecular Quantitative structure–activity relationship Molecular model Stereochemistry Clinical Biochemistry Substituent Pharmaceutical Science Quantitative Structure-Activity Relationship Biochemistry chemistry.chemical_compound Polarizability Grind Drug Discovery Anthranilic acid Animals Computer Simulation ortho-Aminobenzoates Molecular Biology Molecular Structure QSAR Organic Chemistry Rats Receptor Cholecystokinin A chemistry Lipophilicity Molecular Medicine Hydrophobic and Hydrophilic Interactions Protein Binding |
| Zdroj: | Bioorganicmedicinal chemistry. 17(14) |
| ISSN: | 1464-3391 |
| Popis: | A research is presented on quantitative structure-activity relationship (QSAR) studies on the more recent class of non-peptidic CCK(1) receptor antagonists. Our results suggest that the balance of hydrophobicity and volume dependent polarizability term plays a key role in the antagonism of CCK(1) receptor. The size of the substitution of ligands at particular position which induce steric fit is crucial as well as their hydrophobic contribution. Indicator variables were used after the best model was found to account for the usual structural features. The CoMFA results show a good variance explanation and the best self-predictivity is slightly lower than 60% with both leave-one-out and random-group methods. The CoMFA molecular fields showed the importance of steric hindrance of the substituent. From the GRIND models it can be deduced that the shape differences of the molecules are secondary in the regulation of the activity, or better, that their polar substituents are capable of occupying the same zones of the space in the most of the cases. |
| Databáze: | OpenAIRE |
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