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New nonpeptide angiotensin II receptor antagonists. 1. Synthesis, biological properties and structure-activity relationships of 2-alkylbenzimidazole derivatives
- Source :
- Journal of Medicinal Chemistry. 35:877-885
- Publication Year :
- 1992
- Publisher :
- American Chemical Society (ACS), 1992.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....6ad48f5186c1940dd36b2bbe4718c863