Benzenesulfohydroxamic acid (Piloty's acid) was functionalized on the hydroxyl group with the N,N-diethylcarbamoyl group, and the hydroxylamine nitrogen was substituted with acetyl (1a), pivaloyl (1b), benzoyl (1c), and ethoxycarbonyl (1d) groups. Only compound 1d inhibited yeast aldehyde dehydrogenase (AlDH) in vitro (IC(50) 169 microM). When administered to rats, 1d significantly raised blood acetaldehyde levels following ethanol challenge, thus serving as a diethylcarbamoylating/nitroxylating, dual action inhibitor of AlDH in vivo. A more potent dual action agent was N-(N, N-diethylcarbamoyl)-O-methylbenzenesulfohydroxamic acid (5c), which was postulated to release diethylcarbamoylnitroxyl (9), a highly potent diethylcarbamoylating/nitroxylating agent, following metabolic O-demethylation in vivo. The dual action inhibition of AlDH exhibited by 1d, and especially 9, constitutes a merger of the mechanism of action of the alcohol deterrent agents, disulfiram and cyanamide.

中文翻译：

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作为乙醛脱氢酶的双重作用抑制剂的二乙基氨基甲酰化/硝基氧基化剂：双硫仑-氰胺合并。

在N，N-二乙基氨基甲酰基的羟基上官能化苯甲磺酸异羟肟酸（Piloty's acid），羟胺氮被乙酰基（1a），新戊酰基（1b），苯甲酰基（1c）和乙氧基羰基（1d）取代。只有化合物1d体外抑制了酵母醛脱氢酶（AlDH）（IC（50）169 microM）。当对大鼠给药时，1d乙醇攻击后1d会显着提高血液乙醛水平，因此在体内可作为AlDH的二乙基氨基甲酰化/亚硝酰化的双重作用抑制剂。一种更有效的双作用剂是N-（N，N-二乙基氨基甲酰基）-O-甲基苯磺基异羟肟酸（5c），假定它在体内代谢O-去甲基化后释放出二乙基氨基甲酰硝基氧（9），一种高效的二乙基氨基甲酰化/硝基氧化剂。 。