Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/325922
Type: Artigo
Title: New 2-aminothiazoline Derivatives Lower Blood Pressure Of Spontaneously Hypertensive Rats (shr) Via I-1-imidazoline And Alpha-2 Adrenergic Receptors Activation
New 2-aminothiazoline derivatives lower blood pressure of spontaneously hypertensive rats (shr) via I-1-imidazoline and alpha-2 adrenergic receptors activation
Author: Ferreira, Renan B.
Oliveira, Mariana G. de
Antunes, Edson
Almeida, Wanda P.
Ibrahim, Badr M.
Abdel-Rahman, Abdel A.
Abstract: 2-Aminothiazolines share an isosteric relationship with imidazolines and oxazolines with antihypertensive activity mainly mediated by the imidazoline I-1-receptor. In the present work, we have prepared five aminothiazolines, following a previously described synthetic pathway. Aminothiazolines derived from dicyclo-propylmethylamine (ATZ1) and cyclohexylamine (3) are unprecedented in the literature. Competitive radioligand assay was carried out with all synthetic compounds, and the I-1 receptor affinity in comparison to rilmenidine in PC12 cells was determined. Surprisingly, the rilmenidine isoster (ATZ1) showed no I-1-receptor interaction. Diethyl (ATZ4) and 2-ethyl-hexylamine (ATZ5) derivatives bind to the receptor with 11.98 and 10.94 nmol/l, respectively. These compounds were selected for in vivo experiments. Both compounds reduced the blood pressure of spontaneously hypertensive rats (SHR). The hypotensive effect of these compounds was abrogated in the presence of a(2) adrenergic (yohimbine) and I-1 (efaroxan) receptor antagonists suggesting that both aminothiazolines bind to the adrenergic and imidazoline receptors. Lipinski's descriptors of the synthesized aminothiazolines were calculated and are similar to the known imidazoline I-1 receptor ligands. 3D-Similarity between ATZ5 and agmatine, the natural imidazoline receptor ligand, was also observed.
2-Aminothiazolines share an isosteric relationship with imidazolines and oxazolines with antihypertensive activity mainly mediated by the imidazoline I-1-receptor. In the present work, we have prepared five aminothiazolines, following a previously described synthetic pathway. Aminothiazolines derived from dicyclo-propylmethylamine (ATZ1) and cyclohexylamine (3) are unprecedented in the literature. Competitive radioligand assay was carried out with all synthetic compounds, and the I-1 receptor affinity in comparison to rilmenidine in PC12 cells was determined. Surprisingly, the rilmenidine isoster (ATZ1) showed no I-1-receptor interaction. Diethyl (ATZ4) and 2-ethyl-hexylamine (ATZ5) derivatives bind to the receptor with 11.98 and 10.94 nmol/l, respectively. These compounds were selected for in vivo experiments. Both compounds reduced the blood pressure of spontaneously hypertensive rats (SHR). The hypotensive effect of these compounds was abrogated in the presence of a(2) adrenergic (yohimbine) and I-1 (efaroxan) receptor antagonists suggesting that both aminothiazolines bind to the adrenergic and imidazoline receptors. Lipinski's descriptors of the synthesized aminothiazolines were calculated and are similar to the known imidazoline I-1 receptor ligands. 3D-Similarity between ATZ5 and agmatine, the natural imidazoline receptor ligand, was also observed
Subject: Imidazoline Receptor
Aminothiazoline
Hypertension
Pc12 Cells
Binding Assay
Hipertensão
Células PC12
Receptores de imidazolinas
Country: Países Baixos
Editor: Elsevier
Citation: Euroepan Journal Of Pharmacology. Elsevier Science Bv, v. 791, p. 803 - 810, 2016.
Rights: fechado
Identifier DOI: 10.1016/j.ejphar.2016.10.009
Address: http://www.sciencedirect.com/science/article/pii/S0014299916306501
Date Issue: 2016
Appears in Collections:IQ - Artigos e Outros Documentos
FCM - Artigos e Outros Documentos

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