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Cyclization-activated prodrugs. Basic carbamates of 4-hydroxyanisole.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1990 Jan; Vol. 33 (1), pp. 97-101. - Publication Year :
- 1990
-
Abstract
- A series of basic carbamates of 4-hydroxyanisole was prepared and evaluated as progenitors of this melanocytotoxic phenol. All of the carbamates were relatively stable at low pH but released 4-hydroxyanisole cleanly at pH 7.4 at rates that were structure dependent. A detailed study of the N-methyl-N-[2-(methylamino)ethyl]carbamate showed that generation of the parent phenol followed first-order kinetics with t1/2 = 36.3 min at pH 7.4, 37 degrees C, and was accompanied by formation of N,N'-dimethylimidazolidinone. These basic carbamates are examples of cyclization-activated prodrugs in which generation of the active drug is not linked to enzymatic cleavage but rather depends solely upon a predictable, intramolecular cyclization-elimination reaction.
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 33
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 2296038
- Full Text :
- https://doi.org/10.1021/jm00163a016