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Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives.

Abstract：

:A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives, albeit being structurally more closely related to prazosin, were devoid of this property. The most active derivative, N-[3-[(4-amino-6, 7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarbo xamide hydrochloride, alfuzosin (12), showed high selectivity for peripheral alpha 1-postjunctional adrenoceptors. At equiactive antihypertensive doses, its effect on the pressor response to postural changes in conscious dog was less marked than that shown by prazosin. In the light of these results, alfuzosin was selected for clinical evaluation.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Manoury PM,Binet JL,Dumas AP,Lefèvre-Borg F,Cavero I

doi

10.1021/jm00151a003

subject

Has Abstract

pub_date

1986-01-01 00:00:00

pages

19-25

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

29

pub_type

杂志文章

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