Design and synthesis of nonpeptide angiotensin II receptor antagonists featuring acyclic imidazole-mimicking structural units.
Extensive molecular modelling studies, including conformational analysis and the comparison of molecular electrostatic potential distributions, wee used to evaluate structural parameters of new antagonists containing acyclic replacements of the N = C-N imidazole region. The synthesis and the biological screening of a series of acyl biphenyltetrazole derivatives were planned and realized to gain an insight into the structure-activity relationships of this unusual class of Angiotensin II antagonists.
Angiolini
M
M
University of Milano, Organic and Industrial Chemistry Department, C.N.R. Centre for the Study of Organic and Natural Compounds, Italy.
Belvisi
L
L
Poma
D
D
Salimbeni
A
A
Sciammetta
N
N
Scolastico
C
C
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000737:chemistry; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D019808:Losartan / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D055672:Static Electricity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000737:chemistry; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D019808:Losartan