2-(Anilinomethyl)imidazolines as α1-adrenoceptor agonists: the identification of α1A subtype selective 2′-carboxylic acid esters and amides

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Abstract

2-(Anilinomethyl)imidazolines with 2′-esters or 2′-amides are potent agonists of the cloned human α1-adrenoceptors in vitro. The size and shape of the ortho substituent can have significant effects on the potency, efficacy, and subtype selectivity of these 2-(anilinomethyl)imidazolines. α1A-subtype selective agonists have been identified.

2-(Anilinomethyl)imidazolines with 2′-esters or 2′-amides are potent agonists of the cloned human α1-adrenoceptors in vitro. The identification of α1A subtype selective agonists is reported.

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Cited by (7)

  • Synthesis and biological activities of 2-[(heteroaryl)methyl]imidazolines

    2012, Bioorganic and Medicinal Chemistry
    Citation Excerpt :

    For example, 2-(anilino)imidazolines such as clonidine and its analogues (structure A, Fig. 1) are non-selective α2-adrenoceptor/I1 receptor agonists widely used in clinical practice for the treatment of hypertension and in intensive care units as sedative, anxiolytic and analgesic agents, while other analogues of clonidine with a methylene bridge connecting the imidazoline ring with an aromatic moiety, represented by, for example, tolazoline (structure B), are α1-adrenoceptor antagonists which behave as vasodilators. On the other hand, cirazoline with a methylenoxy spacer (structure C, X = O) is known to behave as an α1-adrenoceptor agonist and an α2 antagonist with vasoconstricting properties, and a series of 2-(anilinomethyl)imidazolines of type C (X = NH) has been described as potent α1-adrenoreceptor agonists useful for the treatment of benign prostatic hyperplasia.5–8 Recently, we have disclosed a highly selective imidazoline-based partial α2-adrenoceptor agonist marsanidine (1-[(imidazolidin-2-yl)imino]indazole, compound D, Fig. 1), from which emerged 7-methyl-marsanidine9 and its positional analogues E,10 compounds with potent hypotensive and diuretic activities.

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