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Synthesis and receptor binding activity of novel 5-((Tetrazole-5yl)- phenyl) thiophenes

Lovrić, Marija; Tvrdeić, Ante; Cepanec, Ivica; Litvić, Mladen
Synthesis and receptor binding activity of novel 5-((Tetrazole-5yl)- phenyl) thiophenes // Periodicum Biologorum 115 (2013) Suppl 3 ; 80
Zagreb, Hrvatska, 2013. (poster, domaća recenzija, sažetak, znanstveni)

Synthesis and receptor binding activity of novel 5-((Tetrazole-5yl)- phenyl) thiophenes

Lovrić, Marija ; Tvrdeić, Ante ; Cepanec, Ivica ; Litvić, Mladen

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Periodicum Biologorum 115 (2013) Suppl 3 ; 80 / - , 2013

7th Croatian Congress of Pharmacology with International participation

Mjesto i datum
Zagreb, Hrvatska, 18-21. 09. 2013

Vrsta sudjelovanja

Vrsta recenzije
Domaća recenzija

Ključne riječi
Angiotensin II (AII) AT1 receptors; 5-[2-(tetrazole-5-yl)phenyl]thiophenes; receptor binding

Introduction Angiotensin II receptor antagonists (sartans) are a new class of pharmacological agents for treatment of hypertension. They act as selective blockers (antagonists) of the most potent vasoconstrictor, angiotensin II (AII) AT1 receptors. Aiming to explain the influence of the structural changes on the biological activity, the synthesis and the receptor binging activity of structural analogues of sartan, derivatives of 5-[2-(tetrazole-5- yl)phenyl]thiophene is described. Materials and methods The novel sustituted heterobiaryls were efficiently prepared by multistep synthesis starting from methyl 2-aminobenzoate. Receptor binding activity of the newly synthesized compounds was tested on glomeruli isolated from rat kidney cortex using radioactively labelled angiotensin II ([3H]AII). Obtained results were compared with the commercially antihypertensive drug valsartan. Results Modification of Gomberg-Bachmann-Hey reaction was proved to be a convenient method for the preparation of multigram scale synthesis of target intermediate 2-(5-Formyl-thiophen-2- yl)benzonitrile. Further synthesis included reductive amination, acylation, tetrazole formation and finally the removal of protecting ester function. In all binding experiments angiotensin II displaced [3H]AII binding to isolated rat glomeruli in concentration 10 µM. Non-specific binding did not occur in more than 40% of [3H]AII total binding. In concentrations ranging from 1 nM to 10 μM, AII and valsartan inhibited completely the binding of [3H]AII on AT1 receptors from isolated rat glomeruli. Novel 5-[2-(tetrazole-5-yl)phenyl]thiophene derivatives were found to be two orders of magnitude less active than valsartan. Conclusions Replacement of the central phenyl ring of the biphenyl moiety of valsartan with a heteroaromatic thiophene decreases the binding affinity and inhibitory effect of the compounds.

Izvorni jezik

Znanstvena područja
Kemija, Temeljne medicinske znanosti


Projekt / tema
108-2192382-2369 - Melatonin i angiotenzin II u farmakologiji boli i hipertenzije (Ante Tvrdeić, )

Medicinski fakultet, Zagreb

Časopis indeksira:

  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus