Understanding DP receptor antagonism using a CoMSIA approach
| Autor: | David Stefany, Ali Ardati, Harris Keith John, Aguiar Joacy C, Roy J. Vaz, Ashfaq Parkar, Lim Sungtaek, Yi Li, Tim Gillespy, Gardner Charles J, Lan Mu, Robert Marcus, Cao Bin, Isabelle Morize, Dragan A. Cirovic |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Dp receptor Quantitative structure–activity relationship Training set Molecular model Chemistry Stereochemistry Receptors Prostaglandin Organic Chemistry Clinical Biochemistry Aminopyridines Quantitative Structure-Activity Relationship Pharmaceutical Science Hydrogen Bonding Biochemistry Drug Discovery Humans Molecular Medicine Receptors Immunologic Antagonism Molecular Biology Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 21:66-75 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2010.11.071 |
| Popis: | A Comparative Molecular Similarity Indices Analysis (CoMSIA) was performed for 2,6-substituted-4-monosubstituted aminopyrimidine antagonists of prostaglandin D(2) receptor (DP). Both two-component (Q(2) = 0.63, R(2) = 0.82, SEE = 0.47 pIC(50)) and three-component (Q(2) = 0.70, R(2) = 0.91, SEE = 0.36 pIC(50)) CoMSIA models were established. Two hydrogen-bond acceptors with spatial separation of about 8Å are shown as optimal for binding. A large hydrophobic center that separates the two acceptors confers to the potency of the 2,6-substituted-4-monosubstituted aminopyrimidine. The models were used to predict IC(50) values for compounds which had functional groups different from those in the training set. |
| Databáze: | OpenAIRE |
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