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 Department of Chemistry, University of Patras, Patras 26500, Greece 2 Eldrug S.A., Patras Science Park, Patras 26504, Greece 3 Department of Pharmacology, School of Medicine, University of Patras, Patras 26500, Greece 4 Department of Internal Medicine, 'ATTIKON' University Hospital, Athens 12462, Greece 5 Department of Chemistry, University of Athens, Athens 15771, Greece
* Authors to whom correspondence should be addressed.
Received: 24 April 2013; in revised form: 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

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MDPI and ACS Style

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.

AMA Style

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(7):7510-7532.

Chicago/Turabian Style

Agelis, George; Kelaidonis, Konstantinos; Resvani, Amalia; Kalavrizioti, Dimitra; Androutsou, Maria-Eleni; Plotas, Panagiotis; Vlahakos, Demetrios; Koukoulitsa, Catherine; Tselios, Theodore; Mavromoustakos, Thomas; Matsoukas, John. 2013. "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 18, no. 7: 7510-7532.

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