Guanidine and 2-Aminoimidazoline Aromatic Derivatives as a2-Adrenoceptor Ligands: Searching for Structure-Activity Relationships

  1. Rodriguez, F. 13
  2. Rozas, I. 1
  3. Ortega, J.E. 24
  4. Erdozain, A.M. 24
  5. Meana, J.J. 24
  6. Callado, L.F. 24
  1. 1 University College Dublin
    info

    University College Dublin

    Dublín, Irlanda

    ROR https://ror.org/05m7pjf47

  2. 2 Centro de Investigacion Biomedica en Red de Salud Mental
    info

    Centro de Investigacion Biomedica en Red de Salud Mental

    Madrid, España

    ROR https://ror.org/009byq155

  3. 3 Universidad de La Rioja
    info

    Universidad de La Rioja

    Logroño, España

    ROR https://ror.org/0553yr311

  4. 4 Universidad del País Vasco/Euskal Herriko Unibertsitatea
    info

    Universidad del País Vasco/Euskal Herriko Unibertsitatea

    Lejona, España

    ROR https://ror.org/000xsnr85

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Journal:
Journal of Medicinal Chemistry

ISSN: 0022-2623

Year of publication: 2009

Volume: 52

Issue: 3

Pages: 601-609

Type: Article

DOI: 10.1021/JM800838R PMID: 19133776 SCOPUS: 2-s2.0-61449164022 GOOGLE SCHOLAR

More publications in: Journal of Medicinal Chemistry

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Abstract

In this paper, we report the synthesis of three new 2-aminoimidazoline (compounds 4b, 5b, and 6b) and three new guanidine derivatives (compounds 7b, 8b, and 9b) as potential α2-adrenoceptor antagonists for the treatment of depression. Their pharmacological profile was evaluated in vitro in human brain tissue and compared to the potential antidepressant 1 and the agonists 2 and 3. All new substrates were evaluated by in vitro functional [35S]GTPyS binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Compound 8b was found to be an antagonist in vitro and was subjected to in vivo microdialysis experiments in rats. Moreover, a new synthesis of the precursor amines for compounds 4b-9b is presented. © 2009 American Chemical Society.