Novel calcium antagonists. Synthesis and structure-activity relationship studies of benzothiazoline derivatives.
J Med Chem
; 31(5): 919-30, 1988 May.
Article
em En
| MEDLINE
| ID: mdl-3361580
ABSTRACT
A series of novel compounds having a benzothiazoline skeleton was studied for their structure-activity relationship (SAR) with respect to Ca2+ antagonistic activity. As test compounds, analogues of 3-acyl-2-arylbenzothiazolines (3) were synthesized. Benzothiazoline derivatives (3) exerted higher Ca2+ antagonistic activity than the corresponding thiazolidine derivatives (2). Effects of substituents R1-R4, the substitution position of the aminoalkoxy group and R2, and the length of the methylene chain on biological activities were examined. Compound 4 [3-acetyl-2-[5-methoxy-2-[4-[N-methyl-N-(3,4,5-trimethoxyphenethyl ) amino]butoxy]phenyl]benzothiazoline hydrochloride] showed a potent Ca2+ antagonistic activity in vitro and dual inhibition on the fast Na+ inward channel and the slow Ca2+ inward channel in Langendorff perfused rabbit hearts. Compound 4 also showed a long-acting hypotensive effect in spontaneously hypertensive rats and prevented acute pulmonary thrombotic death in mice.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiazóis
/
Bloqueadores dos Canais de Cálcio
Limite:
Animals
Idioma:
En
Ano de publicação:
1988
Tipo de documento:
Article