Despite the isolation of hundreds of bioactive isocyanides from terrestrial fungi and bacteria as well as marine organisms, the isocyanide functionality has so far received little attention from a medicinal chemistry standpoint. The widespread tenet that isocyanides are chemically and metabolically unstable has restricted bioactivity studies to their antifouling properties and technical applications. In order to confirm or refute this idea, the hepatic metabolism of six model isocyanides was investigated. Aromatic and primary isocyanides turned out to be unstable and metabolically labile, but secondary and tertiary isocyanides resisted metabolization, showing, in some cases, cytochrome P450 inhibitory properties. The potential therefore exists for the secondary and tertiary isocyanides to qualify them as pharmacophore groups, in particular as war-heads for metalloenzyme inhibition because of their potent metal-coordinating properties.

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异氰酸酯部分的代谢命运：异氰酸酯药理基团是否被药物化学家所忽视？

尽管从陆地真菌和细菌以及海洋生物中分离出了数百种生物活性异氰化物，但从药用化学的角度来看，迄今为止，异氰化物的功能很少受到关注。异氰酸酯在化学和代谢上不稳定的普遍信条将生物活性研究局限于其防污性能和技术应用。为了证实或反驳这一想法，研究了六种模型异氰酸酯的肝代谢。芳香族和初级异氰酸酯不稳定且代谢不稳定，但次级和叔异氰酸酯抗代谢，在某些情况下显示出细胞色素P450的抑制特性。因此，存在仲异氰酸酯和叔异氰酸酯使其成为药效团基团的潜力，