NO-releasing hybrids of cardiovascular drugs

Current Medicinal Chemistry
A MartelliV Calderone

Abstract

Nitric oxide (NO) is an endogenous compound, which plays a fundamental role in the modulation of the function of the cardiovascular system, where it induces vasorelaxing and antiplatelet responses, mainly through the stimulation of guanylate cyclase and the increase of cGMP. Many drugs of common, time-honoured clinical use (for example, glycerol trinitrate and all the vasodilator nitrites and nitrates) act via the release of exogenous NO, thus mimicking the effects of the endogenous factor. In the last few years, a revision of the "one-compound-one-target" paradigm has led pharmacologists and pharmaceutical chemists to develop new classes of molecules which combine different pharmacodynamic properties. This innovative pharmacological/pharmaceutical strategy has produced hybrid drugs, with a dual mechanism of action: a) the slow release of nitric oxide and b) another fundamental pharmacodynamic profile. These drugs have been obtained by inserting appropriate NO-donor chemical groups (i.e. nitrate esters, nitrosothiols, etc.), linked to a known drug, by means of a variable spacer moiety. These new pharmacodynamic hybrids present the advantage of combining a basic mechanism of action (for example, cyclooxygenase inhibition, beta-a...Continue Reading

Citations

Jan 18, 2012·Journal of Medicinal Chemistry·Jun WangJohn F Gilmer
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Jan 20, 2016·Journal of Peptide Science : an Official Publication of the European Peptide Society·Iwona WinieckaDaniel Sokulski
Feb 2, 2008·The Journal of Pharmacy and Pharmacology·Vincenzo CalderoneAldo Balsamo
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Mar 15, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Modesto de CandiaCosimo D Altomare
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Dec 2, 2020·Expert Opinion on Drug Discovery·Alma MartelliVincenzo Calderone
Jul 17, 2020·Journal of Medicinal Chemistry·José Marco-Contelles, Yihua Zhang

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