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Synthesis and antitrypanosomal activity of some bis(4-guanylphenyl) five- and six-membered ring heterocycles.

Abstract：

:2,5-Bis(4-guanylphenyl)-1,3-oxazole, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole and -1,3,4-thiadiazole, and 3,6-bis(4-guanylphenyl)pyridazine and several of their "cyclic guanyl" analogues have been synthesized. 2,5-Bis(4-guanylphenyl)-1,3-oxazole and -1,3,4-thiadiazole showed good activity, whithout acute toxicity, against Trypanosoma rhodesiense in mice, producing cures at a 3 mg/kg dosage level. This activity is comparable to stilbamidine, hydroxystilbamidine, and pentamidine in this test. In contrast, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole shows a sharp reduction in activity in our test system. Generally, the cyclic guanyl analogues exhibit low orders of activity, and toxicity begins to appear at moderate dosage levels. All guanyl and cyclic guanyl compounds were synthesized from bisnitrile precursors by way of imidate ester hydrochlorides in a classical Pinner-type approach.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Das BP,Wallace RA,Boykin DW Jr

doi

10.1021/jm00179a022

subject

Has Abstract

pub_date

1980-05-01 00:00:00

pages

578-81

issue

5

eissn

0022-2623

issn

1520-4804

journal_volume

23

pub_type

杂志文章

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