European Journal of Medicinal Chemistry p. 467 - 477 (1990)
Update date:2022-08-05
Topics:
Barraclough, P.
Beams, R. M.
Black, J. W.
Cambridge, D.
Collard, D.
et al.
Aryl-substituted benzimidazole, imidazopyridine, imidazopyrazine, imidazopyridazine, oxazolopyridine, purine, pyrollopyridine and thiazolopyridine derivatives have been prepared and evaluated as inotropic agents.Purine 8 and the 1H-imidazo<4,5-c>- and <4,5-d>pyridazines 9 and 10 proved to be of most interest, having similar in vivo inotropic potencies to sulmazole.The pKa's, protonation sites and lipophilicities for most heterocycles were determined experimentally and some of their electronic properties calculated.For a subset of active heterocycles a correlation was observed between in vitro inotropism and the charge density of the imidazo nitrogen adjacent to the electrostatic potential minimum.Structure-activity relationships are discussed in some detail.
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