| Autor: |
Saari WS; Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486., Schwering JE, Lyle PA, Smith SJ, Engelhardt EL |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1990 Jan; Vol. 33 (1), pp. 97-101. |
| DOI: |
10.1021/jm00163a016 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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