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Selective angiotensin II AT(2) receptor agonists devoid of the imidazole ring system
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
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2007 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 15, no 22, 7166-7183 p.Article in journal (Refereed) Published
Abstract [en]

A versatile parallel synthetic method to obtain three series of non-cyclic analogues of the first drug-like selective angiotensin II AT2 receptor agonist (1) has been developed. In analogy with the transformation of losartan to valsartan it was demonstrated that a non-cyclic moiety could be employed as an imidazole replacement to obtain AT2 selective compounds. In all the three series, AT2 receptor ligands with affinities in the lower nanomolar range were found. None of the analogues exhibited any affinity for the AT1 receptor. Four compounds, 17, 22, 39 and 51, were examined in a neurite outgrowth cell assay. All four compounds were found to exert a high agonistic effect as deduced from their capacity to induce neurite elongation in neuronal cells, as does angiotensin II.

Place, publisher, year, edition, pages
2007. Vol. 15, no 22, 7166-7183 p.
Keyword [en]
Agonist, Angiotensin, AT2
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-16621DOI: 10.1016/j.bmc.2007.07.026ISI: 000250324900029PubMedID: 17825570OAI: oai:DiVA.org:uu-16621DiVA: diva2:44392
Available from: 2008-05-29 Created: 2008-05-29 Last updated: 2017-12-08Bibliographically approved

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Botros, MiladKarlén, AndersHallberg, MathiasAlterman, Mathias

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