Electrostatic Potential of a New Angiotensin II Receptor Antagonist from X-ray Diffraction and Ab Initio Calculations
| Autor: | Laura Belvisi, Riccardo Destro, Raffaella Soave, Carlo Scolastico |
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| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: | |
| Zdroj: | Electron, Spin and Momentum Densities and Chemical Reactivity, edited by Mezey, P.G.; Robertson, Beverly E., pp. 275–283. Hingham, Massachusetts: Kluwer Academic Pub, 2000 info:cnr-pdr/source/autori:Raffaella Soave, Riccardo Destro, Laura Belvisi, Carlo Scolastico/titolo:Electrostatic Potential of a New Angiotensin II Receptor Antagonist from X-ray Diffraction and Ab Initio Calculations/titolo_volume:Electron, Spin and Momentum Densities and Chemical Reactivity/curatori_volume:Mezey, P.G.; Robertson, Beverly E./editore: /anno:2000 Understanding Chemical Reactivity ISBN: 0792360850 |
| Popis: | The hormone angiotensin II (AII), an octapeptide of sequence Asp-Arg-Val-TyrIle-His-Pro-Phe produced by the renin–angiotensin system (RAS), participates in a number of physiological functions associated with the regulation of blood pressure. Drugs that inhibit the RAS have been shown to be effective in treating human hypertension [1]. A possible approach to interfering with the RAS is to inhibit the binding of AII to its receptor, and recent pharmacological research is currently directed towards non-peptide AII receptor antagonists that, unlike peptide AII receptor inhibitors, can exhibit oral activity, long-plasma half-life and no partial agonism. In a recent paper by Salimbeni et al. [2], a novel series of such AII antagonists has been presented: on the basis of a comparative analysis of theoretical distributions of the electrostatic potential ( (r)) of active and inactive compounds and overlay studies, employing a computational model of an AII active conformation, it was found that the compound named LR-B/081 [3, 4] (C30H30N6O3S), i.e. 2[(6-butyl-2-methyl-4-oxo-5-{4-[2-(1H-tetrazol-5-yl)phenyl] benzyl}-3H-pyrimidin3-yl)methyl]-3-thiophenecarboxylate (Scheme 1), was one of the most potent in the series, and was selected as a candidate for further studies. |
| Databáze: | OpenAIRE |
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