In eons of evolution, isocyanides carved out a niche in the ecological systems probably thanks to their metal coordinating properties. In 1859 the first isocyanide was synthesized by humans and in 1950 the first natural isocyanide was discovered. Now, at the beginning of XXI century, hundreds of isocyanides have been isolated both in prokaryotes and eukaryotes and thousands have been synthesized in the laboratory. For some of them their ecological role is known, and their potent biological activity as antibacterial, antifungal, antimalarial, antifouling, and antitumoral compounds has been described. Notwithstanding, the isocyanides have not gained a good reputation among medicinal chemists who have erroneously considered them either too reactive or metabolically unstable, and this has restricted their main use to technical applications as ligands in coordination chemistry. The aim of this review is therefore to show the richness in biological activity of the isocyanide-containing molecules, to support the idea of using the isocyanide functional group as an unconventional pharmacophore especially useful as a metal coordinating warhead. The unhidden hope is to convince the skeptical medicinal chemists of the isocyanide potential in many areas of drug discovery and considering them in the design of future drugs.

中文翻译：

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异氰化物的药物化学

在漫长的进化过程中，异氰化物在生态系统中占据了一席之地，这可能要归功于它们的金属配位特性。1859 年人类合成了第一个异氰化物，1950 年发现了第一个天然异氰化物。现在，在二十一世纪初，已经在原核生物和真核生物中分离出数百种异氰化物，并在实验室合成了数千种。对于它们中的一些，它们的生态作用是已知的，并且它们作为抗菌、抗真菌、抗疟疾、防污和抗肿瘤化合物的有效生物活性已被描述。尽管如此，异氰化物在药物化学家中并没有获得良好的声誉，他们错误地认为它们太活泼或代谢不稳定，这限制了它们在配位化学中作为配体的技术应用的主要用途。因此，本综述的目的是展示含异氰化物分子的丰富生物活性，以支持将异氰化物官能团用作非常规药效团的想法，特别适用于金属配位弹头。隐藏的希望是让持怀疑态度的药物化学家相信异氰化物在药物发现的许多领域的潜力，并在未来药物的设计中考虑它们。