New antianginal nitro esters with reduced hypotensive activity. Synthesis and pharmacological evaluation of 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones.
J Med Chem
; 38(1): 130-6, 1995 Jan 06.
Article
em En
| MEDLINE
| ID: mdl-7837224
ABSTRACT
New nitro ester 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones show marked inhibitory activity against ischemia-induced electrocardiographic changes, with only limited systemic hemodynamic effects, and are reported in the present study. These new nitro vasodilators are potent inhibitors of the electrocardiographic T-wave and S-T segment elevation induced by intravenous or intracoronary administration of Arg-vasopressin or methacholine in the anesthetized rat. The most active compounds are up to 300- and 600-fold more potent than glyceryl trinitrate or Nicorandil, respectively. These nitro esters relax in a concentration-dependent manner the isolated rabbit aorta, at higher concentrations (2-40-fold) than glyceryl trinitrate, and reduce the mean arterial blood pressure at doses 7-300-fold higher than those required by glyceryl trinitrate to exert a similar hypotensive effect. Remarkably, these compounds retain their anti-ischemic and hemodynamic profile after oral (po) administration. These new nitro ester derivatives, endowed with a marked antianginal activity, which is not associated with concurrent and pronounced falls in systemic blood pressure, represent the leads of a new class of selective nitrovasodilators having a preferential action on large coronary vessels, which could be clinically relevant in the treatment of coronary artery diseases.
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Base de dados:
MEDLINE
Assunto principal:
Oxazinas
/
Pressão Sanguínea
/
Angina Pectoris
/
Nitratos
Limite:
Animals
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Itália