Nonpeptide angiotensin II receptor antagonists. 1. Synthesis and in vitro structure-activity relationships of 4-[[[(1H-pyrrol-1-ylacetyl)amino]phenyl]methyl]imidazole derivatives as angiotensin II receptor antagonists
| العنوان: | Nonpeptide angiotensin II receptor antagonists. 1. Synthesis and in vitro structure-activity relationships of 4-[[[(1H-pyrrol-1-ylacetyl)amino]phenyl]methyl]imidazole derivatives as angiotensin II receptor antagonists |
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| المؤلفون: | Terry C. Major, Ila Sircar, Robert L. Panek, Gina H. Lu, R. Thomas Winters, John Quin |
| المصدر: | Journal of Medicinal Chemistry. 36:1735-1745 |
| بيانات النشر: | American Chemical Society (ACS), 1993. |
| سنة النشر: | 1993 |
| مصطلحات موضوعية: | Male, Models, Molecular, Angiotensin receptor, Stereochemistry, medicine.drug_class, Carboxylic acid, Molecular Conformation, Carboxamide, Angiotensin Receptor Antagonists, Structure-Activity Relationship, chemistry.chemical_compound, Residue (chemistry), Drug Discovery, medicine, Animals, Moiety, Imidazole, Pyrroles, Pyrrole, chemistry.chemical_classification, Receptors, Angiotensin, Molecular Structure, Angiotensin II, Cell Membrane, Imidazoles, Rats, Liver, chemistry, Molecular Medicine, Rabbits |
| الوصف: | A novel series of non-biphenylyltetrazole angiotensin II receptor antagonists which contain a 1H-pyrrol-1-ylacetyl residue in place of the benzoyl residue in EXP 6803 have been developed. The receptor binding activity of several members of this new series was in the 10(-8) M range, which was better than that of EXP 6803. Introduction of a carboxylic acid moiety at the 2-position of the pyrrole ring enhanced the in vitro binding affinity at the receptor by 10-fold. Compounds containing an acetic acid (18) or a propionic acid residue (20) at the 5-position of the imidazole were more potent than the carboxylic acid analogue (24). The binding IC50 of the most potent compound 20 was 22 nM. Compounds 18, 20, and 24 in their best fit conformations were manually overlayed on that of the template conformation of EXP 6803 and EXP 8623, respectively. The synthesis and structure-activity relationship data are described. |
| تدمد: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00064a007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99245e897485eb0fbe7359139bb20545 https://doi.org/10.1021/jm00064a007 |
| رقم الانضمام: | edsair.doi.dedup.....99245e897485eb0fbe7359139bb20545 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204804 00222623 |
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| DOI: | 10.1021/jm00064a007 |