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Synthesis, enzymatic hydrolysis and physico-chemical properties of N-substituted 4-(aminomethyl)benzoate diester prodrugs of ganciclovir.
Acta Pharm Nord 1991; 3(4):243-7AP

Abstract

Various N-substituted 4-(aminomethyl)benzoate diesters of ganciclovir were synthesized and evaluated as prodrug forms with the aim of improving the delivery characteristics of ganciclovir. The esters were hydrolyzed enzymatically by human plasma to the parent drug, the hydrolysis proceeding through formation of the corresponding monoester. The nature of the amino substituents had a marked influence on the rate of enzymatic hydrolysis, the most enzymatically labile ester being the 4-(morpholinomethyl)benzoate derivative. All esters were more lipophilic than ganciclovir in terms of octanol-pH 7.4 buffer partition coefficients. These properties combined with good aqueous solubility and high chemical stability in weakly acidic solutions make the N-substituted 4-(aminomethyl)benzoate diesters a promising prodrug type for ganciclovir to enhance its delivery characteristics for e.g. parenteral administration.

Authors+Show Affiliations

Royal Danish School of Pharmacy, Department of Pharmaceutical Chemistry, Copenhagen.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1781915

Citation

Jensen, E, and H Bundgaard. "Synthesis, Enzymatic Hydrolysis and Physico-chemical Properties of N-substituted 4-(aminomethyl)benzoate Diester Prodrugs of Ganciclovir." Acta Pharmaceutica Nordica, vol. 3, no. 4, 1991, pp. 243-7.
Jensen E, Bundgaard H. Synthesis, enzymatic hydrolysis and physico-chemical properties of N-substituted 4-(aminomethyl)benzoate diester prodrugs of ganciclovir. Acta Pharm Nord. 1991;3(4):243-7.
Jensen, E., & Bundgaard, H. (1991). Synthesis, enzymatic hydrolysis and physico-chemical properties of N-substituted 4-(aminomethyl)benzoate diester prodrugs of ganciclovir. Acta Pharmaceutica Nordica, 3(4), pp. 243-7.
Jensen E, Bundgaard H. Synthesis, Enzymatic Hydrolysis and Physico-chemical Properties of N-substituted 4-(aminomethyl)benzoate Diester Prodrugs of Ganciclovir. Acta Pharm Nord. 1991;3(4):243-7. PubMed PMID: 1781915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, enzymatic hydrolysis and physico-chemical properties of N-substituted 4-(aminomethyl)benzoate diester prodrugs of ganciclovir. AU - Jensen,E, AU - Bundgaard,H, PY - 1991/1/1/pubmed PY - 1991/1/1/medline PY - 1991/1/1/entrez SP - 243 EP - 7 JF - Acta pharmaceutica Nordica JO - Acta Pharm Nord VL - 3 IS - 4 N2 - Various N-substituted 4-(aminomethyl)benzoate diesters of ganciclovir were synthesized and evaluated as prodrug forms with the aim of improving the delivery characteristics of ganciclovir. The esters were hydrolyzed enzymatically by human plasma to the parent drug, the hydrolysis proceeding through formation of the corresponding monoester. The nature of the amino substituents had a marked influence on the rate of enzymatic hydrolysis, the most enzymatically labile ester being the 4-(morpholinomethyl)benzoate derivative. All esters were more lipophilic than ganciclovir in terms of octanol-pH 7.4 buffer partition coefficients. These properties combined with good aqueous solubility and high chemical stability in weakly acidic solutions make the N-substituted 4-(aminomethyl)benzoate diesters a promising prodrug type for ganciclovir to enhance its delivery characteristics for e.g. parenteral administration. SN - 1100-1801 UR - https://www.unboundmedicine.com/medline/citation/1781915/Synthesis_enzymatic_hydrolysis_and_physico_chemical_properties_of_N_substituted_4__aminomethyl_benzoate_diester_prodrugs_of_ganciclovir_ L2 - https://www.lens.org/lens/search?q=citation_id:1781915 DB - PRIME DP - Unbound Medicine ER -