Dipole moment in relation to H2 receptor histamine antagonist activity for cimetidine analogues.
J Med Chem
; 29(1): 44-9, 1986 Jan.
Article
em En
| MEDLINE
| ID: mdl-3941412
ABSTRACT
The activities of a series of H2 receptor histamine antagonists structurally related to cimetidine (1) have been compared to investigate the effect of replacing the cyanoguanidine moiety by other neutral, dipolar groups. Antagonist activity, as measured in vitro on the histamine-stimulated guinea pig right atrium, was found to be very sensitive to relatively minor structural changes. Differences in H2 antagonist activity are accounted for by dipole moment orientation and lipophilicity and are rationalized in terms of an optimum requirement for alignment of a hydrogen-bonding moiety in the antagonist with respect to the receptor and desolvation effects at the receptor. The most active compound in the series is the 2-amino-3-nitropyrrole derivative 5, which combines a near-optimal dipole orientation with high lipophilicity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores Histamínicos
/
Receptores Histamínicos H2
/
Cimetidina
Limite:
Animals
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1986
Tipo de documento:
Article