AAPS PharmSci

, Volume 3, Issue 4, pp 26–29 | Cite as

Electronic and resonance effects on the lonization of structural analogues of efavirenz

  • Shelley R. Rabel
  • Sophie Sun
  • Michael B. Maurin
  • Mona Patel
Article

Abstract

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 pKa value of the cyclic carbamate. The most profound lowering effect on the pKa 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 pKa, 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.

Keywords

pKa Ionization Benzoxazinone Carbamate Solubility Efavirenz Analogs 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Rabel SR, Maurin MB, Rowe SM, Hussain M. Determination of the pKa and pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-Chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3, 1-benzoxazin-2-one (DMP 266). Pharm Dev Tech. 1996;1:91–95.CrossRefGoogle Scholar
  2. 2.
    Bergon M, Bonafos M, Calmon JP. Kinetics of barban dechlorination in an alkaline medium. Agric Biol Chem. 1980;44:1237–1240.CrossRefGoogle Scholar
  3. 3.
    Bergon M, Calmon JP. Structure-reactivity relationships in the hydrolytic degradation of propham, chloropropham, swep and related carbamates. J Agric Food Chem. 1983;31:738–743.CrossRefGoogle Scholar
  4. 4.
    Carey FA, Sundberg RJ. Advanced Organic Chemistry, 2nd ed. New York: Plenum Press; 1984.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2001

Authors and Affiliations

  • Shelley R. Rabel
    • 1
  • Sophie Sun
    • 1
  • Michael B. Maurin
    • 1
  • Mona Patel
    • 2
  1. 1.Pharmacy R&DThe DuPont Pharmaceuticals CompanyWilmington
  2. 2.Chemical and Physical SciencesThe DuPont Pharmaceuticals CompanyWilmington

Personalised recommendations