SYNTHESIS AND BIOLOGICAL-ACTIVITY OF 19-AZASQUALENE 2,3-EPOXIDE AS INHIBITOR OF 2,3-OXIDOSQUALENE CYCLASE

被引：22

作者：

CERUTI, M ^{[1
]}

ROCCO, F ^{[1
]}

VIOLA, F ^{[1
]}

BALLIANO, G ^{[1
]}

GROSA, G ^{[1
]}

DOSIO, F ^{[1
]}

CATTEL, L ^{[1
]}

机构：

[1] FAC FARM TURIN,IST CHIM FARMACEUT APPLICATA,CORSO RAFFAELLO 31,I-10125 TURIN,ITALY

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 28卷 / 09期

关键词：

2,3-OXIDOSQUALENE CYCLASE INHIBITORS; EPOXY AZASQUALENES; HYPOCHOLESTEROLEMICS; ANTIFUNGALS;

D O I：

10.1016/0223-5234(93)90026-B

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

19-Azasqualene 2,3-epoxide and its N-oxide, high-energy intermediate analogue inhibitors of 2,3-oxidosqualene (SO) cyclase, were obtained by total synthesis. These compounds were designed to mimic the C-20 carbonium ion precursor of lanosterol formed during SO cyclization. The synthesis involved the preparation Of C22 squalenoid aldehyde epoxide through a new procedure and the reconstruction of the squalenoid chain bearing a nitrogen at C-19 (pro C-20). 19-Azasqualene 2,3-epoxide was active on SO cyclase from rat and pig liver with an IC50 of 1.5 muM in pig, while in SO cyclases of yeast (S cerevisiae and C albicans) microsomes it was 20-30-fold less active. It was inactive on squalene epoxidase from rat and pig liver at the highest concentrations tested (100 muM).

引用

页码：675 / 682

页数：8

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