New nonpeptide angiotensin II receptor antagonists. 1. Synthesis, biological properties and structure-activity relationships of 2-alkylbenzimidazole derivatives
| Autor: | Arnold Harry Ratcliffe, J. S. Major, Keith Hopkinson Gibson, Christopher P. Allott, Simon Thomas Russell, Brian B. Masek, Andrew Peter Thomas, A. A. Oldham, David A. Roberts, Douglas A. Thomason |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Models Molecular Angiotensin receptor Benzimidazole Stereochemistry Guinea Pigs Molecular Conformation Blood Pressure Binding Competitive Molecular mechanics Angiotensin Receptor Antagonists Structure-Activity Relationship chemistry.chemical_compound In vivo Drug Discovery Animals Structure–activity relationship Molecular Structure Angiotensin II Rats Inbred Strains In vitro Rats chemistry Hypertension Molecular Medicine Benzimidazoles Rabbits hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Medicinal Chemistry. 35:877-885 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00083a011 |
| Popis: | On the basis of an extension of the literature lead 1, a series of benzimidazoles have been synthesized and shown to be angiotensin II (AII) receptor antagonists. The structure-activity relationships of these new antagonists have been explored and the key binding interactions defined. Molecular mechanics calculations were carried out on analogues of imidazole AII antagonists and conformationally restricted analogues were synthesized. The benzimidazole antagonists displaced AII in binding studies in vitro with IC50 values in the range 10(-5)-10(-7) M and antagonized the hypertensive effects of AII in vivo (rats) following intravenous administration with ED50 values in the range of 5-20 mg/kg. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|