Toward beta-aminocarbonyl motifs and nitrogen-susbstituted aromatic heterocycles

由制药公司制造和测试的化合物中，90%以上的结构中至少有一个氮原子，在制药行业中，大约六分之一的反应涉及形成碳-氮键。因此，获取含氮分子的新方法可以通过提供更短和更有效的获取这些化合物的途径来帮助药物发现。许多精细和散装化学品中也含有氮原子。令人惊讶的是，将廉价的石化产品或容易获得的原料(烯烃、炔烃和芳烃)转化为含氮分子目前需要几个步骤，而且更具成本效益和效率的过程是可能和需要的。这种直接过程非常可取，但在工业界和学术界仍然很少使用，尽管世界各地都做出了公认的潜力和密集的研究努力。这项提议将提供针对药品和生物活性天然产品中常见结构元素的这种新技术：β-氨基酮基模体和氮取代杂芳烃。这项研究将受益于与阿斯利康的密切合作，从而最大限度地发挥新技术作为制药研究和开发工具的潜力，并允许合成可能在中枢神经系统(CNS)中显示有趣生物学活动的支架。作为这项研究的一部分，学生将接受非常适合未来药物化学或精细化学品领域工作的培训。

Over 90% of the compounds manufactured and tested by pharmaceutical companies have at least one nitrogen atom in their structure, and approximately one reaction out of six performed in the pharmaceutical industry involves the formation of a carbon-nitrogen bond. As such, new methods to access nitrogen containing molecules can help in drug discovery by providing shorter and more efficient access to these compounds. Many fine and bulk chemicals also incorporate nitrogen atoms. Surprisingly, the conversion of cheap petrochemicals or easily accessible starting materials (alkenes, alkynes and arenes) into nitrogen-containing molecules currently requires several steps and more cost-effective, efficient processes are possible and needed. Such direct processes stand out as highly desirable but remain rarely used in industry and academia, despite well-recognized potential and intense research efforts worldwide. This proposal will provide such new technology targeting common structural elements founds in pharmaceuticals and bioactive natural products: beta-aminocarbonyl motifs and nitrogen-substituted heteroarenes. This research will benefit from a close collaboration with AstraZeneca thus maximizing the potential of such new technologies as tools in pharmaceutical research and development and allowing the synthesis of scaffolds that could display interesting biological activities in the Central Nervous System (CNS). As part of this research, students will receive training that is ideally suited for future work in medicinal chemistry or fine chemicals sectors.