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| Author(s): |
Renan Barroso Ferreira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Química |
| Defense date: | 2012-07-20 |
| Examining board members: |
Wanda Pereira Almeida;
Sergio Pinheiro;
Paulo Cesar Muniz de Lacerda Miranda
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| Advisor: | Wanda Pereira Almeida |
| Abstract | |
Clonidine, a central a2 agonist, is an antihypertensive drug that is in disuse due to undesired effects such as dry mouth, rebound hypertension and withdrawal syndrome. Lately, it is believed that its activity is also due to the stimulation of the imidazolinic receptor (subtype I1) and its undesirable effects are caused by stimulation of the a2-receptor. Since the SNS activity increases with aging, I1 selective drugs is present as an alternative to circumvent hypertensive states due to the increased catecholamine levels, whose production can be mediated by a receptor I1, which structure has no defined yet. In the market, there are two representative 2nd generation antihypertensives of this class, rilmenidine and moxonidine, that have very significant selectivity for I1-receptor, but unwanted effects remain. Although theoretical studies reported in the literature indicate similarity between the properties (geometry, partition coefficients and pKa) of these 2nd generation antihypertensives and a rilmenidine-isoster 2-aminothiazoline, no 2-aminothiazoline was evaluated for its affinity for I1-receptors. Thus, we proposed in this project the synthesis and study of the I1-receptor affinity of 2-aminothiazolines, as potential ligands for these receptors. A series of nine N-alkyl-2-aminothiazolines was synthesized and characterized, in 6 - 50% of yield for three steps, using the S-cyclisation of N-(2-hydroxyethyl)thiourea as synthetic strategy. Studies in vitro showed an interaction between a 2-aminothiazoline and the I1-receptor and in vivo assays with normotensive rats showed no hypotensive effect. Further studies must be done in our laboratory, since some antihypertensive drugs in this class are only active in hypertensive organisms (AU) | |
| FAPESP's process: | 10/03042-8 - SYNTHESIS AND EVALUATION OF 2-AMINOTHIAZOLINES AS POTENCIAL LIGANDS FOR IMIDAZOLINIC RECEPTORS |
| Grantee: | Renan Barroso Ferreira |
| Support Opportunities: | Scholarships in Brazil - Master |