Τίτλος:
The discovery of new potent non-peptide Angiotensin II AT1 receptor blockers:A concise synthesis, molecular docking studies and biological evaluation of N-substituted 5-butylimidazole derivatives.
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
A convenient and facile synthesis, in silico docking studies and in vitro biological evaluation of
N-substituted 5-butylimidazole derivatives as potent Angiotensin II (ANG II) receptor type 1 (AT1)
blockers (ARBs) has been reported in the current study. Our efforts have been directed towards the
development of an efficient synthetic route allowing the facile introduction of substituents on the
imidazole ring. In particular, a series of imidazole based compounds bearing the biphenyl moiety at the
N 1 position, a halogen atom at the C-4 and polar substituents such as hydroxymethyl, aldo or carboxy
group at the C-2 position were designed and synthesized. These compounds were evaluated for binding
to human AT1 receptor and for ANG II antagonism in vitro on isolated rat uterus. Among them, 5-butyl-1-
[[20
-(2H-tetrazol-5-yl)biphenyl-4-yl]methyl]imidazole-2-carboxylic acid (30) exhibited higher binding
affinity compared to the other analogues tested (log IC50 ¼ 8.46). The latter analogue was also found to
be the most active in the rat uterotonic test (pA2 ¼ 7.83). Importantly, the binding affinity was higher to
that of losartan (log IC50 ¼ 8.25) indicating the importance of carboxy group at the C-2 position.
Experimental findings are in good agreement with docking studies, which were undertaken in order to
investigate ligand/AT1 receptor interactions
Συγγραφείς:
G. Agelis, A. Resvani, S. Durdagi, K. Spyridaki , T.Tumová,J. Slaninová, P. Giannopoulos, D. Vlahakos, G. Liapakis,T.Mavromoustakos
Περιοδικό:
European Journal of Medicinal Chemistry
Λέξεις-κλειδιά:
Synthesis Angiotensin II receptor blockers N-substituted 5-butylimidazole derivatives Antihypertensive activity Molecular docking
Κύρια θεματική κατηγορία:
Θετικές Επιστήμες
DOI:
10.1016/j.ejmech.2012.07.040
Αρχείο:
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AggelisEurop2012.pdf
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