NOVEL 1,2-DITHIINS - SYNTHESIS, MOLECULAR MODELING STUDIES, AND ANTIFUNGAL ACTIVITY

被引：49

作者：

BIERER, DE ^{[1
]}

DENER, JM ^{[1
]}

DUBENKO, LG ^{[1
]}

GERBER, RE ^{[1
]}

LITVAK, J ^{[1
]}

PETERLI, S ^{[1
]}

PETERLIROTH, P ^{[1
]}

TRUONG, TV ^{[1
]}

MAO, GH ^{[1
]}

BAUER, BE ^{[1
]}

机构：

[1] BIODATA INC, SAN MATEO, CA 94402 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 14期

关键词：

D O I：

10.1021/jm00014a016

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The first structure-activity study involving the 1,2-dithiin class of compounds (1,2-dithiacyclohexadienes) is herein reported. A series of 3,6-disubstituted 1,2-dithiins was synthesized from dithiins 1d and 1e and evaluated as antifungal agents. A new and versatile synthesis of dithiins 1d and 1e is reported which is amenable to scale-up at the kilogram level. The novelty of the process derives from the use of beta-mercaptopropionitrile as the thiophile, relying on a beta-elimination strategy and subsequent oxidation to create the 1,2-dithiin ring. Optimal geometries of dithiins 1d, 18i, and 45 and model dithiin 61 were determined by molecular mechanics and Hartree-Fock molecular orbital calculations. Two possible mechanisms of action are presented for the 1,2-dithiin class of compounds to explain their observed antifungal activities against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.

引用

页码：2628 / 2648

页数：21

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