Electronic and resonance effects on the lonization of structural analogues of efavirenz
| Autor: | Shelley R. Rabel, Sophie Sun, Mona Patel, Michael B. Maurin |
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| Rok vydání: | 2001 |
| Předmět: |
Cyclopropanes
Ions Carbamate Trifluoromethyl Efavirenz Molecular Structure Stereochemistry medicine.medical_treatment Pharmaceutical Science Hydrogen-Ion Concentration Ring (chemistry) Resonance (chemistry) Medicinal chemistry Article Benzoxazines chemistry.chemical_compound Solubility chemistry Acetylene Alkynes Oxazines Linear Models medicine Molecule |
| Zdroj: | AAPS PharmSci. 3:26-29 |
| ISSN: | 1522-1059 |
| DOI: | 10.1208/ps030428 |
| Popis: | The solubility of 4 analogues of efavirenz was studied as a function of pH. The study evaluated the ionization behavior and determined the relative contribution of electronegative substituents versus resonance effects on the pK(a) value of the cyclic carbamate. The most profound lowering effect on the pK(a) was due to the presence of multiple electronegative substituents and in particular the trifluoromethyl and acetylene groups. The presence of chlorine on the benzoxazinone ring was found to have a slight impact on the pK(a), although to a lesser extent. In the absence of any functional groups on the benzoxazinone ring system, the pKa shifted to a value of 13.2, which is 3 pH units above that of efavirenz and more closely correlates with typical literature values for cyclic carbamates. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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