Cardiotonic agents. 6. Histamine analogues as potential cardiovascular selective H2 agonists.
J Med Chem
; 33(6): 1688-97, 1990 Jun.
Article
in En
| MEDLINE
| ID: mdl-2342063
ABSTRACT
Twenty-six alkyl and aralkyl histamine analogues were prepared as potential cardiotonic agents. Compounds were designed to allow interaction with a putative secondary aryl binding site at the H2 receptor, the presence of which was inferred from the structure of cyprohepatadine, which is known to have H2-antagonist properties. The compounds were examined for inotropic activity in ferret papillary muscle. Potent inotropic activity was generally found in N-alkyl- and N,N-dialkylimidazole-4-ethanamines, whereas N-(amidoalkyl)imidazole-4-ethanamines and N-alkylimidazole-4-propanamines were at best weakly active. Five compounds were examined in screens designed to assess hemodynamic effects and gastric acid secretion in vivo. Two of these compounds, alpha-(3-phenyl-2-transpropenyl)-1H-imidazole-4-ethanamine and N-heptyl-1H-imidazole-4-ethanamine, showed positive inotropic activity with minimal effects on heart rate and mean arterial pressure in vivo; however, both compounds were found to stimulate gastric acid secretion. These results demonstrate that selectivity between various H2-receptor-mediated activities can be obtained with substituted histamine analogues.
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Database:
MEDLINE
Main subject:
Receptors, Histamine H2
/
Cardiotonic Agents
/
Drug Design
/
Histamine
/
Gastric Acid
Limits:
Animals
Language:
En
Year:
1990
Type:
Article