Imidazolines belong to a numerous and long known family of compounds with wide therapeutic applications. They are the active ingredients of many antiallergic, antihypertensive, antidiabetic, sympatholytic, analgetic and anxiety-relieving drugs. The therapeutic potential of these agents is mediated by two types of receptors: α₂-adrenoceptors and I-receptors. According to the most recent hypothesis three types of imidazoline receptors (I₁, I₂, I₃ ) in Rostral Ventrolateral Medulla (a part of medulla oblongata) and in peripheral tissues mediate the desired actions of imidazoline like drugs, and the α₂-adrenoceptors are mainly responsible for the side effects [1].

In early 90thies agmatine, a decarboxylated metabolite of arginine, that was long known to be synthesized in plants, bacteria, many invertebrates and fish [2], was discovered in mammalian tissues [3,4]. This natural polyamine was proposed as an endogenous ligand of the I-receptors and a novel neurotransmitter in mammalian brain [3,5].

Agmatine affects also several other receptors (NMDA, nicotinic, 5-HT) and enzymes (NOS, ODC). This diversity of molecular targets is responsible for various biological properties of agmatine: antihypertensive, antidiabetic, anticonvulsant, antidepressant, antinociceptive, antiapoptotic [6].

We have developed a hypothesis, that compilation of the imidazoline ring and the structure of agmatine (the natural ligand of imidazoline receptors) into one formula, may improve biological properties of the resultant compounds. The final compounds are 4(5)-derivatives of previously unpublished imidazolines.

In this work the synthetic approach and the biological evaluation of this group of compounds will be presented.

References:
[1] G. A. Head; D. N. Mayorov; Cardiovasc. Hematol. Agents Med. Chem. 2006; 4; 17 – 32;
[2] C. W. Tabor; H. Tabor; Ann. Rev. Biochem. 1984; 53; 749 – 790;
[3] G. Li. S. Regunathan; C. J. Barrow; J. Eshraghi; R. Cooper; D. J. Reis; Science; 1994; 263; 966 – 969;
[4] W. Raasch; S. Regunathan; G. Li; D. J. Reis; Life Sci. 1995; 56; 2319 – 2330;
[5] D. J. Reis; S. Regunathan; TiPS; 2000; 21; 187 – 193;
[6] A. Grillo; S. Colombatto; Amino Acids; 2004; 26; 3 – 8;

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