133909-97-4Relevant articles and documents
1,(3,)5-substituted imidazoles, useful in the treatment of hypertension and methods for their preparation
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Paragraph 0171, (2016/03/04)
The present invention provides novel 1,5 and 1,3,5-substituted imidazole compounds in hydrophilic or lipophilic form, which are useful as angiotensin II ATI receptor antagonists suitable for transdermal delivery. The invention also provides pharmaceutical compositions containing such compounds, processes and intermediates for preparing compounds and their use in methods of treating hypertension and cardiovascular diseases.
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.
Synthesis of novel biphenyltetrazole derivatives containing 5-methylisoxazole substituted 1,2,4-triazole
Sun, De-Guang,Hui, Xin-Ping,Xu, Peng-Fei,Zhang, Zi-Yi,Guan, Zuo-Wu
, p. 795 - 801 (2008/02/12)
An efficient route to synthesize the target compounds was developed. Fifteen new 5-[4′-(5-isoxazol-4-aryl-1,2,4-triazol-3-yl-sulfanylmethyl)- biphenyl-2-yl]-tetrazoles derivatives were synthesized. The structures of the new compounds synthesized were confirmed by elemental analyses and spectral data.