| Autor: |
Aalt Bast, Giuseppe Bietti, Hendrik Timmerman, Arturo Donetti, E. Cereda, Antonio Giachetti, Rosamaria Micheletti |
| Rok vydání: |
1988 |
| Předmět: |
|
| Zdroj: |
European Journal of Medicinal Chemistry. 23:267-273 |
| ISSN: |
0223-5234 |
| DOI: |
10.1016/0223-5234(88)90009-8 |
| Popis: |
Studies on protonation of the amidino group present in mifentidine have shown that this H2-receptor antagonist exists predominantly as a formamidinium monocation (95.3%) at physiological pH. Further studies on the preferred conformation by quantum mechanics and molecular mechanics methods have led us to formulate the hypothesis that the active population at the H2-receptor is the monoprotonated form. In order to answer the question, whether the imidazole in mifentidine plays the same role as that present in cimetidine, a number of bioisosteric replacements of this moiety have been performed on the two prototype molecules and their effects tested comparatively in in vitro functional and ligand-binding studies. The results of the study allow the conclusion to be drawn that the role played by the imidazole of mifentidine in blocking the H2-receptor is different from that played by the same group in cimetidine. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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