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Novel calcium antagonists. Synthesis and structure-activity relationship studies of benzothiazoline derivatives.

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Yamamoto K,Fujita M,Tabashi K,Kawashima Y,Kato E,Oya M,Iso T,Iwao J

doi

10.1021/jm00400a006

subject

Has Abstract

pub_date

1988-05-01 00:00:00

pages

919-30

issue

5

eissn

0022-2623

issn

1520-4804

journal_volume

31

pub_type

杂志文章

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