3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the alpha(2)-adrenoceptor compared to the imidazoline I(1) receptor.

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Saczewski F, Kornicka A, Hudson AL, Laird S, Scheinin M, Laurila JM, Rybczynska A, Boblewski K, Lehmann A, Gdaniec M

3-[(Imidazolidin-2-yl)imino]indazole ligands with selectivity for the alpha(2)-adrenoceptor compared to the imidazoline I(1) receptor.

Bioorg Med Chem. 2011 Jan 1;19(1):321-9. doi: 10.1016/j.bmc.2010.11.020. Epub 2010 Nov 11.

PubMed ID

21129985 [ View in PubMed

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Abstract

A series of 3-[(4,5-dihydroimidazolidin-2-yl)imino]indazoles has been synthesized as positional analogues of marsanidine, a highly selective alpha(2)-adrenoceptor ligand. Parent compound 4a and its 4-chloro (4c) and 4-methyl (4d) derivatives display alpha(2)-adrenoceptor affinity at nanomolar concentrations (K(i)=39.4, 15.9 and 22.6nM, respectively) and relatively high alpha(2)/I(1) selectivity ratios of 82, 115 and 690, respectively. Evidence was obtained that these compounds act as partial agonists at alpha(2A)-adrenoceptors. Compound 4d with intrinsic activity comparable with that of marsanidine, but lower than that of clonidine, elicited pronounced cardiovascular effects in anesthetized rats at doses as low as 0.01mg/kg iv.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Clonidine	Alpha-2A adrenergic receptor	EC 50 (nM)	28	N/A	N/A	Details
Dexmedetomidine	Alpha-2A adrenergic receptor	EC 50 (nM)	1.5	N/A	N/A	Details
Norepinephrine	Alpha-2A adrenergic receptor	EC 50 (nM)	110	N/A	N/A	Details