Evaluation of the cyclopentane-1,2-dione as a potential bio-isostere of the carboxylic acid functional group
| Autor: | Carlo Ballatore, Bryant Gay, Longchuan Huang, Katie Herbst Robinson, Michael J. James, John Q. Trojanowski, Virginia M.-Y. Lee, Kurt R. Brunden, Amos B. Smith |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Stereochemistry Isostere medicine.drug_class Carboxylic acid Clinical Biochemistry Carboxylic Acids Pharmaceutical Science Cyclopentanes Crystallography X-Ray Biochemistry Article Receptors Thromboxane A2 Prostaglandin H2 chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Moiety Humans Molecular Biology chemistry.chemical_classification Sulfonamides Dose-Response Relationship Drug Molecular Structure Hydrogen bond Chemistry Organic Chemistry Receptor antagonist Tautomer Propanoic acid Functional group Molecular Medicine |
| Popis: | Cycloalkylpolyones hold promise in drug design as carboxylic acid bio-isosteres. To investigate cyclopentane-1,2-diones as potential surrogates of the carboxylic acid functional group, the acidity, tautomerism, and geometry of hydrogen bonding of representative compounds were evaluated. Prototypic derivatives of the known thromboxane A2 prostanoid (TP) receptor antagonist, 3-(3-(2-((4-chlorophenyl)sulfonamido)-ethyl)phenyl)propanoic acid, in which the carboxylic acid moiety is replaced by the cyclopentane-1,2-dione unit, were synthesized and evaluated as TP receptor antagonists. Cyclopentane-1,2-dione derivative 9 was found to be a potent TP receptor antagonist with an IC50 value comparable to that of the parent carboxylic acid. These results indicate that the cyclopentane-1,2-dione may be a potentially useful carboxylic acid bio-isostere. |
| Databáze: | OpenAIRE |
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