دورية أكاديمية
Cyclization-activated prodrugs. Basic carbamates of 4-hydroxyanisole.
| العنوان: | Cyclization-activated prodrugs. Basic carbamates of 4-hydroxyanisole. |
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| المؤلفون: | Saari WS; Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486., Schwering JE, Lyle PA, Smith SJ, Engelhardt EL |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 1990 Jan; Vol. 33 (1), pp. 97-101. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print Cited Medium: Print ISSN: 0022-2623 (Print) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Prodrugs*, Anisoles/*chemical synthesis , Carbamates/*chemical synthesis, Animals ; Anisoles/pharmacology ; Carbamates/pharmacology ; Chemical Phenomena ; Chemistry ; Cyclization ; Drug Stability ; Hydrogen-Ion Concentration ; Kinetics ; Magnetic Resonance Spectroscopy ; Melanocytes/drug effects ; Mice ; Molecular Structure |
| مستخلص: | 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. |
| المشرفين على المادة: | 0 (Anisoles) 0 (Carbamates) 0 (Prodrugs) 6HT8U7K3AM (mequinol) |
| تواريخ الأحداث: | Date Created: 19900101 Date Completed: 19900222 Latest Revision: 20190709 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1021/jm00163a016 |
| PMID: | 2296038 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0022-2623 |
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| DOI: | 10.1021/jm00163a016 |