Synthesis and insecticidal activity of novel pyrimidine derivatives containing urea pharmacophore against Aedes aegypti

Abstract

BACKGROUND Aedes aegypti is a major mosquito vector for the transmission of serious diseases, especially dengue and yellow fever. More than 1 billion people in developing countries are at risk. The widespread and continual use of pesticides can lead to resistant mosquitoes. In order to maintain mosquito control gains, it is critical to develop and evaluate novel bioactive molecules that differ in mode of action from currently used products. RESULTS A series of novel pyrimidine derivatives were designed and synthesized. Their structures were elucidated by proton nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. The biological activities of these compounds were tested against Ae. aegypti. Many of them exhibited insecticidal activity against adult and larval mosquitoes. Compound 4d displayed relatively good activity to reach 70% mortality at 2 µg mL⁻¹. Furthermore, density functional theory calculations were established to study the structure–activity relationship of these novel compounds. CONCLUSION A practical synthetic route for pyrimidine derivatives is presented. This study suggests that these pyrimidine derivatives exhibit some activity against the yellow fever mosquito and, with further structure modification, could be novel lead compounds for the development of insecticides against mosquitoes. © 2016 Society of Chemical Industry