Selective Carboxylesterase Inhibitors for Improving Efficacy, Safety and Rational use of Ester-Containing Drugs

  • N.P. Boltneva Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
  • G.F. Makhaeva Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severny proezd, Moscow region, Chernogolovka, 142432 Russia
  • E.V. Shchegol’kov Postovsky Institute of Organic Synthesis, Urals Branch of Russian Academy of Sciences, 22/20, S. Kovalevskoy/Akademicheskaya str., Yekaterinburg, 620990 Russia
  • Ya.V. Burgart Postovsky Institute of Organic Synthesis, Urals Branch of Russian Academy of Sciences, 22/20, S. Kovalevskoy/Akademicheskaya str., Yekaterinburg, 620990 Russia
  • V.I. Saloutin Postovsky Institute of Organic Synthesis, Urals Branch of Russian Academy of Sciences, 22/20, S. Kovalevskoy/Akademicheskaya str., Yekaterinburg, 620990 Russia
Keywords: carboxylesterases, prodrugs, ester-containing drugs, inhibitors, polyfluoroalkyl-2-imino-1,3-dione scaffold


In clinical practice, a large number of prodrugs and active drugs containing an ester, carbamate or amide moiety are used. Carboxylesterase (CaE, EC is the key enzyme of hydrolytic metabolism of such drugs in the body, it largely determines their pharmacokinetics, bioavailability, efficacy and possible toxic effects. Using CaE selective inhibitors as components of combined drug therapy it is possible us to regulate the rate of hydrolytic transformation of ester-containing drugs and opens the possibility of their rational use. The development of effective and selective CaE inhibitors suitable for in vivo application is a new promising approach in medicinal chemistry and pharmacology that allows to improve the efficacy, bioavailability and reduce the side effects of ester-containing drugs.


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