New 1,4-dihydropyridines endowed with NO-donor and calcium channel agonist properties.

Abstract:

:A new series of calcium channel agonists structurally related to Bay K8644, containing NO donor furoxans and the related furazans unable to release NO, is described. The racemic mixtures were studied for their action on L-type Ca(2+) channels expressed in cultured rat insulinoma RINm5F cells. All the products proved to be potent calcium channel agonists. All the racemic mixtures, with the only exception of the carbamoyl derivatives 9, 12 endowed with scanty solubility, were separated by chiral chromatography into the corresponding enantiomers; the (+) enantiomers were found to be potent agonists while the (-) ones were feeble antagonists. The racemic mixtures were also assessed for their positive inotropic activity on electrically stimulated rat papillary muscle and for their ability to increase Ca(2+) entry into the vascular smooth muscle of rat aorta strips. The cyanofuroxan 8 proved to be an interesting product with dual Ca(2+)-dependent positive inotropic and NO-dependent vasodilating activity.

journal_name

J Med Chem

authors

Visentin S,Rolando B,Di Stilo A,Fruttero R,Novara M,Carbone E,Roussel C,Vanthuyne N,Gasco A

doi

10.1021/jm031109v

keywords:

subject

Has Abstract

pub_date

2004-05-06 00:00:00

pages

2688-93

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

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