Pirali Tracey, Galli Ubaldina, Serafini Marta, Griglio Alessia, Genazzani Armando A, Tron Gian Cesare
Dipartimento di Scienze del Farmaco, Università del Piemonte Orientale, Novara, Italy.
Methods Mol Biol. 2019;1987:207-221. doi: 10.1007/978-1-4939-9446-5_13.
Multicomponent transformations, such as Ugi and Passerini reactions, allow for the fast synthesis of libraries of medium complexity, avoiding the formation of waste residues and significantly reducing time and money expenditure. Although the Ugi reaction has found a vast number of uses in medicinal chemistry, the employment of the Passerini reaction has received scant attention due to the formation of an α-acyloxyamide, which hardly resists the hydrolytic enzymes in the body. On the other hand, an overlooked possibility with the Passerini products is to exploit the presence of an ester group in the design and synthesis of soft drugs. We started to fill this gap, designing and synthesizing a series of TRPV1 and TRPM8 agonists able to act as soft drugs by using the Passerini reaction.
多组分反应，如乌吉反应和帕瑟里尼反应，能够快速合成中等复杂度的化合物库，避免产生废渣，并显著减少时间和金钱的支出。尽管乌吉反应在药物化学中有广泛应用，但由于帕瑟里尼反应会生成α-酰氧基酰胺，这种产物很难抵抗体内的水解酶，因此该反应的应用受到的关注较少。另一方面，帕瑟里尼反应产物存在一个被忽视的可能性，即在软药的设计和合成中利用酯基的存在。我们开始填补这一空白，通过帕瑟里尼反应设计并合成了一系列能够作为软药发挥作用的TRPV1和TRPM8激动剂。
