155092-07-2Relevant academic research and scientific papers
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
Agelis, George,Resvani, Amalia,Matsoukas, John,Durdagi, Serdar,Spyridaki, Katerina,Liapakis, George,Tumova, Tereza,Slaninova, Jirina,Giannopoulos, Panagiotis,Mavromoustakos, Thomas,Vlahakos, Demetrios
, p. 358 - 374,17 (2020/07/30)
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-[[2′-(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 = 8.46). The latter analogue was also found to be the most active in the rat uterotonic test (pA2 = 7.83). Importantly, the binding affinity was higher to that of losartan (-log IC50 = 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.
Imidazole based non-peptide angiotensin II receptor antagonists. Investigation of the effects of the orientation of the imidazole ring on biological activity
Wahhab,Smith,Ganter,Moore,Hondrelis,Matsoukas,Moore
, p. 1157 - 1168 (2007/10/02)
Non-peptide angiotensin II receptor antagonists related to losartan (DuP 753, CAS 114798-26-4) were prepared and evaluated for antagonist activity in the rat isolated uterus assay. The synthetic strategy concentrated on changes in the orientation of the imidazole ring relative to the substituents, which were maintained in a similar pattern to that found in losartan. The results indicate that biological activity of such antagonists shows little dependence on the orientation of the imidazole ring, but that the spacing of the substituents is of primary importance.
