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Molecules 2013, 18(7), 7510-7532; doi:10.3390/molecules18077510
Article

Facile and Efficient Syntheses of a Series of N-Benzyl and N-Biphenylmethyl Substituted Imidazole Derivatives Based on (E)-Urocanic acid, as Angiotensin II AT1 Receptor Blockers

1,2,* , 1,2, 1,2, 3, 1,2, 2,3, 4, 5, 1, 5 and 1,2,*
Received: 24 April 2013 / Revised: 17 June 2013 / Accepted: 20 June 2013 / Published: 27 June 2013
(This article belongs to the Section Medicinal Chemistry)
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Abstract

In the present work, a facile and efficient route for the synthesis of a series of N-substituted imidazole derivatives is described. Docking studies have revealed that N-substituted imidazole derivatives based on (E)-urocanic acid may be potential antihypertensive leads. Therefore, new AT1 receptor blockers bearing either the benzyl or the biphenylmethyl moiety at the N-1 or N-3 position, either the (E)-acrylate or the propanoate fragment and their related acids at the C-4 position as well as a halogen atom at the C-5 position of the imidazole ring, were synthesized. The newly synthesized analogues were evaluated for binding to human AT1 receptor. The biological results showed that this class of molecules possesses moderate or no activity, thus not always confirming high docking scores. Nonetheless, important conclusions can be derived for their molecular basis of their mode of action and help medicinal chemists to design and synthesize more potent ones. An aliphatic group as in losartan seems to be important for enhancing binding affinity and activity.
Keywords: synthesis; AT1 receptor blockers; (E)-urocanic acid; N-alkylation; docking studies synthesis; AT1 receptor blockers; (E)-urocanic acid; N-alkylation; docking studies
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Agelis, G.; Kelaidonis, K.; Resvani, A.; Kalavrizioti, D.; Androutsou, M.-E.; Plotas, P.; Vlahakos, D.; Koukoulitsa, C.; Tselios, T.; Mavromoustakos, T.; Matsoukas, J. Facile and Efficient Syntheses of a Series of N-Benzyl and N-Biphenylmethyl Substituted Imidazole Derivatives Based on (E)-Urocanic acid, as Angiotensin II AT1 Receptor Blockers. Molecules 2013, 18, 7510-7532.

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