Dynamic NMR study and theoretical calculations on the conformational exchange of valsartan and related compounds
(c) 2007 John Wiley & Sons, Ltd.
| Publié dans: | Magnetic resonance in chemistry : MRC. - 1985. - 45(2007), 11 vom: 09. Nov., Seite 929-36 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , , |
| Format: | Article |
| Langue: | English |
| Publié: |
2007
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| Accès à la collection: | Magnetic resonance in chemistry : MRC |
| Sujets: | Journal Article Research Support, Non-U.S. Gov't Antihypertensive Agents Butyrates Morpholines Tetrazoles Valsartan 80M03YXJ7I Valine HG18B9YRS7 |
| Résumé: | (c) 2007 John Wiley & Sons, Ltd. Valsartan (1), an antihypertensive drug of the sartan family, and three related compounds, 3-methyl-2-((2'-(1-methyl-1H-tetrazol-5-yl)biphenyl-4-ylmethyl) pentanoylamino)butyric acid (2), 3-isopropyl-6-propyl-4-(2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl) morpholine-2,5-dione (3), and 3-isopropyl-6-propyl-4-(4'-(1H-tetrazol-5-yl)biphenyl4-ylmethyl) morpholine-2,5-dione (4), were studied by nuclear magnetic resonance (NMR) spectroscopy. Assignment of (1)H and (13)C NMR resonances for the compounds were completed using COSY, HSQC and HMBC techniques. It was found that each of the compounds 1, 2, and 4 had two sets of (1)H and (13)C resonances, suggesting the presence of two conformers in solution. Based on NOESY experiments at different temperatures, thermodynamic parameters of the conformational exchange process were deduced for these compounds. The exchange barrier was found to be 17.9 +/- 0.7, 18.5 +/- 0.8, and 17.7 +/- 0.6 kcal mol(-1) with the corresponding free energy difference (DeltaG) of 0.32 +/- 0.04, 0.23 +/- 0.01, and 0.13 +/- 0.04 kcal mol(-1) for 1, 2, and 4, respectively, at 298 K. Two conformations of valsartan were elucidated by NMR spectroscopy and quantum chemistry calculation. The results showed that two conformers of valsartan interchange via rotation about the C(O)--N bond |
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| Description: | Date Completed 06.12.2007 Date Revised 19.11.2015 published: Print Citation Status MEDLINE |
| ISSN: | 1097-458X |